Trial Watch: Immunotherapy plus radiation therapy for oncological indications

OncoImmunology

Volumn 5, Issue 9, 2016, Pages

  Vacchelli, Erika ^a,b,c,d,e   Bloy, Norma ^a,b,c,d,e   Aranda, Fernando ^f   Buqué, Aitziber ^a,b,c,d,e   Cremer, Isabelle ^a,b,c,d   Demaria, Sandra ^g   Eggermont, Alexander ^e   Formenti, Silvia Chiara ^g   Fridman, Wolf Hervé ^a,b,c,d   Fucikova, Jitka ^h,i   Galon, Jérôme ^a,b,c,d   Spisek, Radek ^h,i   Tartour, Eric ^b,j,k   Zitvogel, Laurence ^a,e   Kroemer, Guido ^{a,b,c,d,e,k,l}   Galluzzi, Lorenzo ^a,b,c,d,e,g  

^a INSERM   (France)

^b UNIVERSITÉ PARIS DESCARTES   (France)

^c SORBONNE UNIVERSITÉ   (France)

^d CENTRE DE RECHERCHE DES CORDELIERS   (France)

^e INSTITUT GUSTAVE ROUSSY   (France)

^f INSTITUT D INVESTIGACIONS BIOMÈDIQUES AUGUST PI I SUNYER IDIBAPS   (Spain)

^g WEILL CORNELL MEDICAL COLLEGE   (United States)

^h Sotio   (Czech Republic)

ⁱ UNIVERSITY HOSPITAL MOTOL   (Czech Republic)

^j PARIS CARDIOVASCULAR RESEARCH CENTER   (France)

^k HÔPITAL EUROPÉEN GEORGES POMPIDOU   (France)

^l KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

more..

Author keywords

Danger associated molecular patterns; immunogenic cell death; ipilimumab; nivolumab; pembrolizumab; TGF 1

Indexed keywords

ADALIMUMAB; ATEZOLIZUMAB; AVELUMAB; CANCER VACCINE; DURVALUMAB; EPIDERMAL GROWTH FACTOR RECEPTOR; FRESOLIMUMAB; IMMUNOMODULATING AGENT; INTERLEUKIN 6; INTERLEUKIN 8; IPILIMUMAB; NANOPARTICLE; NIVOLUMAB; PEMBROLIZUMAB; REACTIVE NITROGEN SPECIES; REACTIVE OXYGEN METABOLITE; TICILIMUMAB; TOLL LIKE RECEPTOR; TOLL LIKE RECEPTOR AGONIST; TRANSFORMING GROWTH FACTOR BETA1; TUMOR NECROSIS FACTOR; VARLILUMAB;

ADAPTIVE IMMUNITY; ANTIGENICITY; BRACHYTHERAPY; BREAST CARCINOMA; CANCER CHEMOTHERAPY; CANCER IMMUNOTHERAPY; CELL CYCLE ARREST; CELL DEATH; DRUG EFFICACY; DRUG SAFETY; ESOPHAGUS CANCER; EXTERNAL BEAM RADIOTHERAPY; HUMAN; IMMUNOGENICITY; LIVER CELL CARCINOMA; MELANOMA; NON SMALL CELL LUNG CANCER; ONCOLYTIC VIROTHERAPY; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PHASE 4 CLINICAL TRIAL (TOPIC); PROSTATE CANCER; RADIATION PROTECTION; RADIOSENSITIZATION; REVIEW; TUMOR ASSOCIATED LEUKOCYTE;

EID: 84986253403     PISSN: 21624011     EISSN: 2162402X     Source Type: Journal    
DOI: 10.1080/2162402X.2016.1214790     Document Type: Review

References (241)

1. J.Bernier, E.J.Hall, A.Giaccia. Radiation oncology:a century of achievements. Nat Rev Cancer 2004; 4:737-47; PMID:15343280; http://dx.doi.org/10.1038/nrc1451
2. J.Thariat, J.M.Hannoun-Levi, A.Sun Myint, T.Vuong, J.P.Gerard. Past, present, and future of radiotherapy for the benefit of patients. Nat Rev Clin Oncol 2013; 10:52-60; PMID:23183635; http://dx.doi.org/10.1038/nrclinonc.2012.203
3. M.Baumann, M.Krause, J.Overgaard, J.Debus, S.M.Bentzen, J.Daartz, C.Richter, D.Zips, T.Bortfeld. Radiation oncology in the era of precision medicine. Nat Rev Cancer 2016; 16:234-49; PMID:27009394; http://dx.doi.org/10.1038/nrc.2016.18
4. D.Schaue, W.H.McBride. Opportunities and challenges of radiotherapy for treating cancer. Nat Rev Clin Oncol 2015; 12:527-40; PMID:26122185; http://dx.doi.org/10.1038/nrclinonc.2015.120
5. G.Delaney, S.Jacob, C.Featherstone, M.Barton. The role of radiotherapy in cancer treatment:estimating optimal utilization from a review of evidence-based clinical guidelines. Cancer 2005; 104:1129-37; PMID:16080176; http://dx.doi.org/10.1002/cncr.21324
6. R.Siegel, C.DeSantis, K.Virgo, K.Stein, A.Mariotto, T.Smith, D.Cooper, T.Gansler, C.Lerro, S.Fedewa et al. Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin 2012; 62:220-41; PMID:22700443; http://dx.doi.org/10.3322/caac.21149
7. W.P.Roos, A.D.Thomas, B.Kaina. DNA damage and the balance between survival and death in cancer biology. Nat Rev Cancer 2016; 16:20-33; PMID:26678314; http://dx.doi.org/10.1038/nrc.2015.2
8. P.A.Perez-Mancera, A.R.Young, M.Narita. Inside and out:the activities of senescence in cancer. Nat Rev Cancer 2014; 14:547-58; PMID:25030953; http://dx.doi.org/10.1038/nrc3773
9. V.M.Bolanos-Garcia. Formation of multiprotein assemblies in the nucleus:the spindle assembly checkpoint. Int Rev Cell Mol Biol 2014; 307:151-74; PMID:24380595; http://dx.doi.org/10.1016/B978-0-12-800046-5.00006-0
10. I.Vitale, L.Galluzzi, M.Castedo, G.Kroemer. Mitotic catastrophe:a mechanism for avoiding genomic instability. Nat Rev Mol Cell Biol 2011; 12:385-92; PMID:21527953; http://dx.doi.org/10.1038/nrm3115
11. L.Galluzzi, J.M.Bravo-San Pedro, G.Kroemer. Organelle-specific initiation of cell death. Nat Cell Biol 2014; 16:728-36; PMID:25082195; http://dx.doi.org/10.1038/ncb3005
12. J.Campisi, F.d'Adda di Fagagna. Cellular senescence:when bad things happen to good cells. Nat Rev Mol Cell Biol 2007; 8:729-40; PMID:17667954; http://dx.doi.org/10.1038/nrm2233
13. C.Mothersill, C.B.Seymour. Radiation-induced bystander effects–implications for cancer. Nat Rev Cancer 2004; 4:158-64; PMID:14964312; http://dx.doi.org/10.1038/nrc1277
14. K.M.Prise, J.M.O'Sullivan. Radiation-induced bystander signalling in cancer therapy. Nat Rev Cancer 2009; 9:351-60; PMID:19377507; http://dx.doi.org/10.1038/nrc2603
15. E.B.Golden, S.C.Formenti. Is tumor (R)ejection by the immune system the “5th R” of radiobiology? Oncoimmunology 2014; 3:e28133; PMID:24800177; http://dx.doi.org/10.4161/onci.28133
16. B.E.Lehnert, E.H.Goodwin, A.Deshpande. Extracellular factor(s) following exposure to alpha particles can cause sister chromatid exchanges in normal human cells. Cancer Res 1997; 57:2164-71; PMID:9187116
17. C.Shao, Y.Furusawa, M.Aoki, H.Matsumoto, K.Ando. Nitric oxide-mediated bystander effect induced by heavy-ions in human salivary gland tumour cells. Int J Radiat Biol 2002; 78:837-44; PMID:12428924; http://dx.doi.org/10.1080/09553000210149786
18. C.Shao, V.Stewart, M.Folkard, B.D.Michael, K.M.Prise. Nitric oxide-mediated signaling in the bystander response of individually targeted glioma cells. Cancer Res 2003; 63:8437-42; PMID:14679007
19. C.H.Chou, P.J.Chen, P.H.Lee, A.L.Cheng, H.C.Hsu, J.C.Cheng. Radiation-induced hepatitis B virus reactivation in liver mediated by the bystander effect from irradiated endothelial cells. Clin Cancer Res 2007; 13:851-7; PMID:17289877; http://dx.doi.org/10.1158/1078-0432.CCR-06-2459
20. P.K.Narayanan, K.E.LaRue, E.H.Goodwin, B.E.Lehnert. Alpha particles induce the production of interleukin-8 by human cells. Radiat Res 1999; 152:57-63; PMID:10381841; http://dx.doi.org/10.2307/3580049
21. R.Iyer, B.E.Lehnert, R.Svensson. Factors underlying the cell growth-related bystander responses to alpha particles. Cancer Res 2000; 60:1290-8; PMID:10728689
22. C.Vanpouille-Box, J.M.Diamond, K.A.Pilones, J.Zavadil, J.S.Babb, S.C.Formenti, M.H.Barcellos-Hoff, S.Demaria. TGFbeta is a master regulator of radiation therapy-induced antitumor immunity. Cancer Res 2015; 75:2232-42; PMID:25858148; http://dx.doi.org/10.1158/0008-5472.CAN-14-3511
23. F.Bouquet, A.Pal, K.A.Pilones, S.Demaria, B.Hann, R.J.Akhurst, J.S.Babb, S.M.Lonning, J.K.DeWyngaert, S.C.Formenti et al. TGFbeta1 inhibition increases the radiosensitivity of breast cancer cells in vitro and promotes tumor control by radiation in vivo. Clin Cancer Res 2011; 17:6754-65; PMID:22028490; http://dx.doi.org/10.1158/1078-0432.CCR-11-0544
24. K.H.Young, M.J.Gough, M.Crittenden. Tumor immune remodeling by TGFbeta inhibition improves the efficacy of radiation therapy. Oncoimmunology 2015; 4:e955696; PMID:25949887; http://dx.doi.org/10.4161/21624011.2014.955696
25. H.Zhou, V.N.Ivanov, J.Gillespie, C.R.Geard, S.A.Amundson, D.J.Brenner, Z.Yu, H.B.Lieberman, T.K.Hei. Mechanism of radiation-induced bystander effect:role of the cyclooxygenase-2 signaling pathway. Proc Natl Acad Sci U S A 2005; 102:14641-6; PMID:16203985; http://dx.doi.org/10.1073/pnas.0505473102
26. L.Galluzzi, J.M.Bravo-San Pedro, I.Vitale, S.A.Aaronson, J.M.Abrams, D.Adam, E.S.Alnemri, L.Altucci, D.Andrews, M.Annicchiarico-Petruzzelli et al. Essential versus accessory aspects of cell death:recommendations of the NCCD 2015. Cell Death Differ 2015; 22:58-73; PMID:25236395; http://dx.doi.org/10.1038/cdd.2014.137
27. E.B.Golden, I.Pellicciotta, S.Demaria, M.H.Barcellos-Hoff, S.C.Formenti. The convergence of radiation and immunogenic cell death signaling pathways. Front Oncol 2012; 2:88; PMID:22891162; http://dx.doi.org/10.3389/fonc.2012.00088
28. E.B.Golden, D.Frances, I.Pellicciotta, S.Demaria, M.Helen Barcellos-Hoff, S.C.Formenti. Radiation fosters dose-dependent and chemotherapy-induced immunogenic cell death. Oncoimmunology 2014; 3:e28518; PMID:25071979; http://dx.doi.org/10.4161/onci.28518
29. L.Galluzzi, A.Buque, O.Kepp, L.Zitvogel, G.Kroemer. Immunological effects of conventional chemotherapy and targeted anticancer agents. Cancer Cell 2015; 28:690-714; PMID:26678337; http://dx.doi.org/10.1016/j.ccell.2015.10.012
30. G.Kroemer, L.Galluzzi, O.Kepp, L.Zitvogel. Immunogenic cell death in cancer therapy. Annu Rev Immunol 2013; 31:51-72; PMID:23157435; http://dx.doi.org/10.1146/annurev-immunol-032712-100008
31. D.V.Krysko, A.D.Garg, A.Kaczmarek, O.Krysko, P.Agostinis, P.Vandenabeele. Immunogenic cell death and DAMPs in cancer therapy. Nat Rev Cancer 2012; 12:860-75; PMID:23151605; http://dx.doi.org/10.1038/nrc3380
32. S.C.Formenti, S.Demaria. Radiation therapy to convert the tumor into an in situ vaccine. Int J Radiat Oncol Biol Phys 2012; 84:879-80; PMID:23078897; http://dx.doi.org/10.1016/j.ijrobp.2012.06.020
33. J.M.Kaminski, E.Shinohara, J.B.Summers, K.J.Niermann, A.Morimoto, J.Brousal. The controversial abscopal effect. Cancer Treat Rev 2005; 31:159-72; PMID:15923088; http://dx.doi.org/10.1016/j.ctrv.2005.03.004
34. S.Demaria, B.Ng, M.L.Devitt, J.S.Babb, N.Kawashima, L.Liebes, S.C.Formenti. Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated. Int J Radiat Oncol Biol Phys 2004; 58:862-70; PMID:14967443; http://dx.doi.org/10.1016/j.ijrobp.2003.09.012
35. M.Z.Dewan, A.E.Galloway, N.Kawashima, J.K.Dewyngaert, J.S.Babb, S.C.Formenti, S.Demaria. Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody. Clin Cancer Res 2009; 15:5379-88; PMID:19706802; http://dx.doi.org/10.1158/1078-0432.CCR-09-0265
36. E.B.Golden, S.Demaria, P.B.Schiff, A.Chachoua, S.C.Formenti. An abscopal response to radiation and ipilimumab in a patient with metastatic non-small cell lung cancer. Cancer Immunol Res 2013; 1:365-72; PMID:24563870; http://dx.doi.org/10.1158/2326-6066.CIR-13-0115
37. S.M.Hiniker, D.S.Chen, S.J.Knox. Abscopal effect in a patient with melanoma. N Engl J Med 2012; 366:2035; author reply -6; PMID:22621637; http://dx.doi.org/10.1056/NEJMc1203984
38. S.Siva, M.P.Macmanus, R.F.Martin, O.A.Martin. Abscopal effects of radiation therapy:a clinical review for the radiobiologist. Cancer Lett 2015; 356(1):82-90; PMID:24125863; http://dx.doi.org/10.1016/j.canlet.2013.09.018
39. S.Goel, D.G.Duda, L.Xu, L.L.Munn, Y.Boucher, D.Fukumura, R.K.Jain. Normalization of the vasculature for treatment of cancer and other diseases. Physiol Rev 2011; 91:1071-121; PMID:21742796; http://dx.doi.org/10.1152/physrev.00038.2010
40. R.K.Jain. Normalization of tumor vasculature:an emerging concept in antiangiogenic therapy. Science 2005; 307:58-62; PMID:15637262; http://dx.doi.org/10.1126/science.1104819
41. E.Tartour, H.Pere, B.Maillere, M.Terme, N.Merillon, J.Taieb, F.Sandoval, F.Quintin-Colonna, K.Lacerda, A.Karadimou et al. Angiogenesis and immunity:a bidirectional link potentially relevant for the monitoring of antiangiogenic therapy and the development of novel therapeutic combination with immunotherapy. Cancer Metastasis Rev 2011; 30:83-95; PMID:21249423; http://dx.doi.org/10.1007/s10555-011-9281-4
42. N.Bloy, J.Pol, G.Manic, I.Vitale, A.Eggermont, J.Galon, E.Tartour, L.Zitvogel, G.Kroemer, L.Galluzzi. Trial Watch:radioimmunotherapy for oncological indications. Oncoimmunology 2014; 3:e954929; PMID:25941606; http://dx.doi.org/10.4161/21624011.2014.954929
43. E.Vacchelli, I.Vitale, E.Tartour, A.Eggermont, C.Sautes-Fridman, J.Galon, L.Zitvogel, G.Kroemer, L.Galluzzi. Trial Watch:anticancer radioimmunotherapy. Oncoimmunology 2013; 2:e25595; PMID:24319634; http://dx.doi.org/10.4161/onci.25595
44. S.S.Ahmad, S.Duke, R.Jena, M.V.Williams, N.G.Burnet. Advances in radiotherapy. BMJ 2012; 345:e7765; PMID:23212681; http://dx.doi.org/10.1136/bmj.e7765
45. V.T.DeVitaJr., T.S.Lawrence, S.A.Rosenberg. Cancer:Principles & Practice of Oncology. Philadelphia:Wolters Kluwer/Lippincott Williams & Wilkins, 2008.
46. B.G.Smaglo, D.Aldeghaither, L.M.Weiner. The development of immunoconjugates for targeted cancer therapy. Nat Rev Clin Oncol 2014; 11:637-48; PMID:25265912; http://dx.doi.org/10.1038/nrclinonc.2014.159
47. M.T.Milano, L.S.Constine, P.Okunieff. Normal tissue tolerance dose metrics for radiation therapy of major organs. Semin Radiat Oncol 2007; 17:131-40; PMID:17395043; http://dx.doi.org/10.1016/j.semradonc.2006.11.009
48. H.B.Stone, C.N.Coleman, M.S.Anscher, W.H.McBride. Effects of radiation on normal tissue:consequences and mechanisms. Lancet Oncol 2003; 4:529-36; PMID:12965273; http://dx.doi.org/10.1016/S1470-2045(03)01191-4
49. A.Trotti, A.D.Colevas, A.Setser, V.Rusch, D.Jaques, V.Budach, C.Langer, B.Murphy, R.Cumberlin, C.N.Coleman et al. CTCAE v3.0:development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol 2003; 13:176-81; PMID:12903007; http://dx.doi.org/10.1016/S1053-4296(03)00031-6
50. B.Emami, J.Lyman, A.Brown, L.Coia, M.Goitein, J.E.Munzenrider, B.Shank, L.J.Solin, M.Wesson. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 1991; 21:109-22; PMID:2032882; http://dx.doi.org/10.1016/0360-3016(91)90171-Y
51. B.A.Jereczek-Fossa, H.R.Marsiglia, R.Orecchia. Radiotherapy-related fatigue. Crit Rev Oncol Hematol 2002; 41:317-25; PMID:11880207; http://dx.doi.org/10.1016/S1040-8428(01)00143-3
52. D.Schaue, E.D.Micewicz, J.A.Ratikan, M.W.Xie, G.Cheng, W.H.McBride. Radiation and inflammation. Semin Radiat Oncol 2015; 25:4-10; PMID:25481260; http://dx.doi.org/10.1016/j.semradonc.2014.07.007
53. L.B.Travis, A.K.Ng, J.M.Allan, C.H.Pui, A.R.Kennedy, X.G.Xu, J.A.Purdy, K.Applegate, J.Yahalom, L.S.Constine et al. Second malignant neoplasms and cardiovascular disease following radiotherapy. J Natl Cancer Inst 2012; 104:357-70; PMID:22312134; http://dx.doi.org/10.1093/jnci/djr533
54. A.Berrington de Gonzalez, R.E.Curtis, S.F.Kry, E.Gilbert, S.Lamart, C.D.Berg, M.Stovall, E.Ron. Proportion of second cancers attributable to radiotherapy treatment in adults:a cohort study in the US SEER cancer registries. Lancet Oncol 2011; 12:353-60; PMID:21454129; http://dx.doi.org/10.1016/S1470-2045(11)70061-4
55. M.Tubiana. Can we reduce the incidence of second primary malignancies occurring after radiotherapy? A critical review. Radiother Oncol 2009; 91:4-15; discussion 1-3; PMID:19201045; http://dx.doi.org/10.1016/j.radonc.2008.12.016
56. B.Movsas, B.Vikram, M.Hauer-Jensen, J.E.Moulder, E.Basch, S.L.Brown, L.A.Kachnic, A.P.Dicker, C.N.Coleman, P.Okunieff. Decreasing the adverse effects of cancer therapy:National Cancer Institute guidance for the clinical development of radiation injury mitigators. Clin Cancer Res 2011; 17:222-8; PMID:21047979; http://dx.doi.org/10.1158/1078-0432.CCR-10-1402
57. L.B.Marks, E.D.Yorke, A.Jackson, R.K.Ten Haken, L.S.Constine, A.Eisbruch, S.M.Bentzen, J.Nam, J.O.Deasy. Use of normal tissue complication probability models in the clinic. Int J Radiat Oncol Biol Phys 2010; 76:S10-9; PMID:20171502; http://dx.doi.org/10.1016/j.ijrobp.2009.07.1754
58. G.C.Barnett, C.M.West, A.M.Dunning, R.M.Elliott, C.E.Coles, P.D.Pharoah, N.G.Burnet. Normal tissue reactions to radiotherapy:towards tailoring treatment dose by genotype. Nat Rev Cancer 2009; 9:134-42; PMID:19148183; http://dx.doi.org/10.1038/nrc2587
59. M.L.Hensley, K.L.Hagerty, T.Kewalramani, D.M.Green, N.J.Meropol, T.H.Wasserman, G.I.Cohen, B.Emami, W.J.Gradishar, R.B.Mitchell et al. American Society of Clinical Oncology 2008 clinical practice guideline update:use of chemotherapy and radiation therapy protectants. J Clin Oncol 2009; 27:127-45; PMID:19018081; http://dx.doi.org/10.1200/JCO.2008.17.2627
60. L.M.Schuchter, M.L.Hensley, N.J.Meropol, E.P.Winer. 2002 update of recommendations for the use of chemotherapy and radiotherapy protectants:clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol 2002; 20:2895-903; PMID:12065567; http://dx.doi.org/10.1200/JCO.2002.04.178
61. D.M.Brizel, T.H.Wasserman, M.Henke, V.Strnad, V.Rudat, A.Monnier, F.Eschwege, J.Zhang, L.Russell, W.Oster et al. Phase III randomized trial of amifostine as a radioprotector in head and neck cancer. J Clin Oncol 2000; 18:3339-45; PMID:11013273
62. J.P.Pouget, I.Navarro-Teulon, M.Bardies, N.Chouin, G.Cartron, A.Pelegrin, D.Azria. Clinical radioimmunotherapy–the role of radiobiology. Nat Rev Clin Oncol 2011; 8:720-34; PMID:22064461; http://dx.doi.org/10.1038/nrclinonc.2011.160
63. E.Y.Huang, F.S.Wang, Y.M.Chen, Y.F.Chen, C.C.Wang, I.H.Lin, Y.J.Huang, K.D.Yang. Amifostine alleviates radiation-induced lethal small bowel damage via promotion of 14-3-3sigma-mediated nuclear p53 accumulation. Oncotarget 2014; 5:9756-69; PMID:25230151; http://dx.doi.org/10.18632/oncotarget.2386
64. S.Demaria, S.C.Formenti. Radiation as an immunological adjuvant:current evidence on dose and fractionation. Front Oncol 2012; 2:153; PMID:23112958; http://dx.doi.org/10.3389/fonc.2012.00153
65. M.Fenton-Kerimian, O.Maisonet, S.C.Formenti. Changes in breast radiotherapy:prone positioning and hypofractionation. Clin J Oncol Nurs 2013; 17:550-3; PMID:24080055; http://dx.doi.org/10.1188/13.CJON.550-553
66. S.Demaria, K.A.Pilones, C.Vanpouille-Box, E.B.Golden, S.C.Formenti. The optimal partnership of radiation and immunotherapy:from preclinical studies to clinical translation. Radiat Res 2014; 182:170-81; PMID:24937779; http://dx.doi.org/10.1667/RR13500.1
67. O.Kepp, L.Senovilla, I.Vitale, E.Vacchelli, S.Adjemian, P.Agostinis, L.Apetoh, F.Aranda, V.Barnaba, N.Bloy et al. Consensus guidelines for the detection of immunogenic cell death. Oncoimmunology 2014; 3:e955691; PMID:25941621; http://dx.doi.org/10.4161/21624011.2014.955691
68. S.C.Formenti, S.Demaria. Combining radiotherapy and cancer immunotherapy:a paradigm shift. J Natl Cancer Inst 2013; 105:256-65; PMID:23291374; http://dx.doi.org/10.1093/jnci/djs629
69. M.Crittenden, H.Kohrt, R.Levy, J.Jones, K.Camphausen, A.Dicker, S.Demaria, S.Formenti. Current clinical trials testing combinations of immunotherapy and radiation. Semin Radiat Oncol 2015; 25:54-64; PMID:25481267; http://dx.doi.org/10.1016/j.semradonc.2014.07.003
70. S.C.Formenti. Immunological aspects of local radiotherapy:clinical relevance. Discov Med 2010; 9:119-24; PMID:20193637
71. M.B.Bernstein, S.Krishnan, J.W.Hodge, J.Y.Chang. Immunotherapy and stereotactic ablative radiotherapy (ISABR):a curative approach? Nat Rev Clin Oncol 2016; 13(8):516-24; PMID:26951040; http://dx.doi.org/10.1038/nrclinonc.2016.30
72. A.Buque, N.Bloy, F.Aranda, F.Castoldi, A.Eggermont, I.Cremer, W.H.Fridman, J.Fucikova, J.Galon, A.Marabelle et al. Trial Watch:Immunomodulatory monoclonal antibodies for oncological indications. Oncoimmunology 2015; 4:e1008814; PMID:26137403; http://dx.doi.org/10.1080/2162402X.2015.1008814
73. S.Mayor. Radiation in combination with immune-checkpoint inhibitors. Lancet Oncol 2015; 16:e162; PMID:25773169; http://dx.doi.org/10.1016/S1470-2045(15)70118-X
74. A.B.Sharabi, M.Lim, T.L.DeWeese, C.G.Drake. Radiation and checkpoint blockade immunotherapy:radiosensitisation and potential mechanisms of synergy. Lancet Oncol 2015; 16:e498-509; PMID:26433823; http://dx.doi.org/10.1016/S1470-2045(15)00007-8
75. C.Vanpouille-Box, K.A.Pilones, E.Wennerberg, S.C.Formenti, S.Demaria. In situ vaccination by radiotherapy to improve responses to anti-CTLA-4 treatment. Vaccine 2015; 33:7415-22; PMID:26148880; http://dx.doi.org/10.1016/j.vaccine.2015.05.105
76. E.W.Newcomb, Y.Lukyanov, N.Kawashima, M.Alonso-Basanta, S.C.Wang, M.Liu, M.Jure-Kunkel, D.Zagzag, S.Demaria, S.C.Formenti. Radiotherapy enhances antitumor effect of anti-CD137 therapy in a mouse Glioma model. Radiat Res 2010; 173:426-32; PMID:20334514; http://dx.doi.org/10.1667/RR1904.1
77. E.Vacchelli, F.Aranda, F.Obrist, A.Eggermont, J.Galon, I.Cremer, L.Zitvogel, G.Kroemer, L.Galluzzi. Trial watch:Immunostimulatory cytokines in cancer therapy. Oncoimmunology 2014; 3:e29030; PMID:25083328; http://dx.doi.org/10.4161/onci.29030
78. S.K.Seung, B.D.Curti, M.Crittenden, E.Walker, T.Coffey, J.C.Siebert, W.Miller, R.Payne, L.Glenn, A.Bageac et al. Phase 1 study of stereotactic body radiotherapy and interleukin-2–tumor and immunological responses. Sci Transl Med 2012; 4:137ra74; PMID:22674552; http://dx.doi.org/10.1126/scitranslmed.3003649
79. K.Yasuda, T.Nirei, N.H.Tsuno, H.Nagawa, J.Kitayama. Intratumoral injection of interleukin-2 augments the local and abscopal effects of radiotherapy in murine rectal cancer. Cancer Sci 2011; 102:1257-63; PMID:21443690; http://dx.doi.org/10.1111/j.1349-7006.2011.01940.x
80. J.Pol, N.Bloy, F.Obrist, A.Eggermont, J.Galon, W.Herve Fridman, I.Cremer, L.Zitvogel, G.Kroemer, L.Galluzzi. Trial Watch:DNA vaccines for cancer therapy. Oncoimmunology 2014; 3:e28185; PMID:24800178; http://dx.doi.org/10.4161/onci.28185
81. J.Pol, N.Bloy, A.Buque, A.Eggermont, I.Cremer, C.Sautes-Fridman, J.Galon, E.Tartour, L.Zitvogel, G.Kroemer et al. Trial Watch:peptide-based anticancer vaccines. Oncoimmunology 2015; 4:e974411; PMID:26137405; http://dx.doi.org/10.4161/2162402X.2014.974411
82. L.Buckel, S.J.Advani, A.Frentzen, Q.Zhang, Y.A.Yu, N.G.Chen, K.Ehrig, J.Stritzker, A.J.Mundt, A.A.Szalay. Combination of fractionated irradiation with anti-VEGF expressing vaccinia virus therapy enhances tumor control by simultaneous radiosensitization of tumor associated endothelium. Int J Cancer 2013; 133:2989-99; PMID:23729266; http://dx.doi.org/10.1002/ijc.28296
83. H.Iinuma, R.Fukushima, T.Inaba, J.Tamura, T.Inoue, E.Ogawa, M.Horikawa, Y.Ikeda, N.Matsutani, K.Takeda et al. Phase I clinical study of multiple epitope peptide vaccine combined with chemoradiation therapy in esophageal cancer patients. J Transl Med 2014; 12:84; PMID:24708624; http://dx.doi.org/10.1186/1479-5876-12-84
84. M.Mondini, M.Nizard, T.Tran, L.Mauge, M.Loi, C.Clemenson, D.Dugue, P.Maroun, E.Louvet, J.Adam et al. Synergy of Radiotherapy and a Cancer Vaccine for the Treatment of HPV-Associated Head and Neck Cancer. Mol Cancer Ther 2015; 14:1336-45; PMID:25833837; http://dx.doi.org/10.1158/1535-7163.MCT-14-1015
85. E.Vacchelli, F.Aranda, A.Eggermont, C.Sautes-Fridman, E.Tartour, E.P.Kennedy, M.Platten, L.Zitvogel, G.Kroemer, L.Galluzzi. Trial watch:IDO inhibitors in cancer therapy. Oncoimmunology 2014; 3:e957994; PMID:25941578; http://dx.doi.org/10.4161/21624011.2014.957994
86. D.Zamarin, M.A.Postow. Immune checkpoint modulation:rational design of combination strategies. Pharmacol Ther 2015; 150:23-32; PMID:25583297; http://dx.doi.org/10.1016/j.pharmthera.2015.01.003
87. F.Aranda, A.Buque, N.Bloy, F.Castoldi, A.Eggermont, I.Cremer, W.H.Fridman, J.Fucikova, J.Galon, R.Spisek et al. Trial Watch:adoptive cell transfer for oncological indications. Oncoimmunology 2015; 4:e1046673; PMID:26451319; http://dx.doi.org/10.1080/2162402X.2015.1046673
88. S.Wei, M.U.Egenti, S.Teitz-Tennenbaum, W.Zou, A.E.Chang. Effects of tumor irradiation on host T-regulatory cells and systemic immunity in the context of adoptive T-cell therapy in mice. J Immunother 2013; 36:124-32; PMID:23377667; http://dx.doi.org/10.1097/CJI.0b013e31828298e6
89. F.Klug, H.Prakash, P.E.Huber, T.Seibel, N.Bender, N.Halama, C.Pfirschke, R.H.Voss, C.Timke, L.Umansky et al. Low-dose irradiation programs macrophage differentiation to an iNOS(+)/M1 phenotype that orchestrates effective T cell immunotherapy. Cancer Cell 2013; 24:589-602; PMID:24209604; http://dx.doi.org/10.1016/j.ccr.2013.09.014
90. J.Pol, N.Bloy, F.Obrist, A.Eggermont, J.Galon, I.Cremer, P.Erbs, J.M.Limacher, X.Preville, L.Zitvogel et al. Trial Watch:oncolytic viruses for cancer therapy. Oncoimmunology 2014; 3:e28694; PMID:25097804; http://dx.doi.org/10.4161/onci.28694
91. J.N.Kyula, A.A.Khan, D.Mansfield, E.M.Karapanagiotou, M.McLaughlin, V.Roulstone, S.Zaidi, T.Pencavel, Y.Touchefeu, R.Seth et al. Synergistic cytotoxicity of radiation and oncolytic Lister strain vaccinia in (V600D/E)BRAF mutant melanoma depends on JNK and TNF-alpha signaling. Oncogene 2014; 33:1700-12; PMID:23624923; http://dx.doi.org/10.1038/onc.2013.112
92. R.F.Chen, Y.Y.Li, L.T.Li, Q.Cheng, G.Jiang, J.N.Zheng. Novel oncolytic adenovirus sensitizes renal cell carcinoma cells to radiotherapy via mitochondrial apoptotic cell death. Mol Med Rep 2015; 11:2141-6; PMID:25411768; http://dx.doi.org/10.3892/mmr.2014.2987
93. W.Wang, M.N.Chen, K.Cheng, L.L.Zhan, J.Zhang. Cytotoxic effect of a combination of bluetongue virus and radiation on prostate cancer. Exp Ther Med 2014; 8:635-41; PMID:25009632; http://dx.doi.org/10.3892/etm.2014.1751
94. F.Aranda, E.Vacchelli, F.Obrist, A.Eggermont, J.Galon, C.Sautes-Fridman, I.Cremer, J.Henrik Ter Meulen, L.Zitvogel, G.Kroemer et al. Trial Watch:Toll-like receptor agonists in oncological indications. Oncoimmunology 2014; 3:e29179; PMID:25083332; http://dx.doi.org/10.4161/onci.29179
95. S.J.Dovedi, M.H.Melis, R.W.Wilkinson, A.L.Adlard, I.J.Stratford, J.Honeychurch, T.M.Illidge. Systemic delivery of a TLR7 agonist in combination with radiation primes durable antitumor immune responses in mouse models of lymphoma. Blood 2013; 121:251-9; PMID:23086756; http://dx.doi.org/10.1182/blood-2012-05-432393
96. S.B.Ye, Z.L.Li, D.H.Luo, B.J.Huang, Y.S.Chen, X.S.Zhang, J.Cui, Y.X.Zeng, J.Li. Tumor-derived exosomes promote tumor progression and T-cell dysfunction through the regulation of enriched exosomal microRNAs in human nasopharyngeal carcinoma. Oncotarget 2014; 5:5439-52; PMID:24978137; http://dx.doi.org/10.18632/oncotarget.2118
97. M.C.Boelens, T.J.Wu, B.Y.Nabet, B.Xu, Y.Qiu, T.Yoon, D.J.Azzam, C.Twyman-Saint Victor, B.Z.Wiemann, H.Ishwaran et al. Exosome transfer from stromal to breast cancer cells regulates therapy resistance pathways. Cell 2014; 159:499-513; PMID:25417103; http://dx.doi.org/10.1016/j.cell.2014.09.051
98. K.Leder, K.Pitter, Q.Laplant, D.Hambardzumyan, B.D.Ross, T.A.Chan, E.C.Holland, F.Michor. Mathematical modeling of PDGF-driven glioblastoma reveals optimized radiation dosing schedules. Cell 2014; 156:603-16; PMID:24485463; http://dx.doi.org/10.1016/j.cell.2013.12.029
99. S.O'Brien, V.M.Golubovskaya, J.Conroy, S.Liu, D.Wang, B.Liu, W.G.Cance. FAK inhibition with small molecule inhibitor Y15 decreases viability, clonogenicity, and cell attachment in thyroid cancer cell lines and synergizes with targeted therapeutics. Oncotarget 2014; 5:7945-59; PMID:25277206; http://dx.doi.org/10.18632/oncotarget.2381
100. B.Tavora, L.E.Reynolds, S.Batista, F.Demircioglu, I.Fernandez, T.Lechertier, D.M.Lees, P.P.Wong, A.Alexopoulou, G.Elia et al. Endothelial-cell FAK targeting sensitizes tumours to DNA-damaging therapy. Nature 2014; 514:112-6; PMID:25079333; http://dx.doi.org/10.1038/nature13541
101. K.H.Vousden, D.P.Lane. p53 in health and disease. Nat Rev Mol Cell Biol 2007; 8:275-83; PMID:17380161; http://dx.doi.org/10.1038/nrm2147
102. M.H.Kubbutat, S.N.Jones, K.H.Vousden. Regulation of p53 stability by Mdm2. Nature 1997; 387:299-303; PMID:9153396; http://dx.doi.org/10.1038/387299a0
103. V.Pant, G.Lozano. Dissecting the p53-Mdm2 feedback loop in vivo:uncoupling the role in p53 stability and activity. Oncotarget 2014; 5:1149-56; PMID:24658419; http://dx.doi.org/10.18632/oncotarget.1797
104. L.A.Tollini, A.Jin, J.Park, Y.Zhang. Regulation of p53 by Mdm2 E3 ligase function is dispensable in embryogenesis and development, but essential in response to DNA damage. Cancer Cell 2014; 26:235-47; PMID:25117711; http://dx.doi.org/10.1016/j.ccr.2014.06.006
105. A.N.Osipov, A.Grekhova, M.Pustovalova, I.V.Ozerov, P.Eremin, N.Vorobyeva, N.Lazareva, A.Pulin, A.Zhavoronkov, S.Roumiantsev et al. Activation of homologous recombination DNA repair in human skin fibroblasts continuously exposed to X-ray radiation. Oncotarget 2015; 6:26876-85; PMID:26337087; http://dx.doi.org/10.18632/oncotarget.4946
106. R.Ceccaldi, J.C.Liu, R.Amunugama, I.Hajdu, B.Primack, M.I.Petalcorin, K.W.O'Connor, P.A.Konstantinopoulos, S.J.Elledge, S.J.Boulton et al. Homologous-recombination-deficient tumours are dependent on Poltheta-mediated repair. Nature 2015; 518:258-62; PMID:25642963; http://dx.doi.org/10.1038/nature14184
107. F.P.Vendetti, A.Lau, S.Schamus, T.P.Conrads, M.J.O'Connor, C.J.Bakkenist. The orally active and bioavailable ATR kinase inhibitor AZD6738 potentiates the anti-tumor effects of cisplatin to resolve ATM-deficient non-small cell lung cancer in vivo. Oncotarget 2015; 6:44289-305; PMID:26517239; http://dx.doi.org/10.18632/oncotarget.6247
108. E.J.Moding, K.D.Castle, B.A.Perez, P.Oh, H.D.Min, H.Norris, Y.Ma, D.M.Cardona, C.L.Lee, D.G.Kirsch. Tumor cells, but not endothelial cells, mediate eradication of primary sarcomas by stereotactic body radiation therapy. Sci Transl Med 2015; 7:278ra34; PMID:25761890; http://dx.doi.org/10.1126/scitranslmed.aaa4214
109. M.Osswald, E.Jung, F.Sahm, G.Solecki, V.Venkataramani, J.Blaes, S.Weil, H.Horstmann, B.Wiestler, M.Syed et al. Brain tumour cells interconnect to a functional and resistant network. Nature 2015; 528:93-8; PMID:26536111; http://dx.doi.org/10.1038/nature16071
110. J.Overgaard. Hypoxic radiosensitization:adored and ignored. J Clin Oncol 2007; 25:4066-74; PMID:17827455; http://dx.doi.org/10.1200/JCO.2007.12.7878
111. T.Reid, B.Oronsky, J.Scicinski, C.L.Scribner, S.J.Knox, S.Ning, D.M.Peehl, R.Korn, M.Stirn, C.A.Carter et al. Safety and activity of RRx-001 in patients with advanced cancer:a first-in-human, open-label, dose-escalation phase 1 study. Lancet Oncol 2015; 16:1133-42; PMID:26296952; http://dx.doi.org/10.1016/S1470-2045(15)00089-3
112. B.Tombal, M.Borre, P.Rathenborg, P.Werbrouck, H.Van Poppel, A.Heidenreich, P.Iversen, J.Braeckman, J.Heracek, E.Baskin-Bey et al. Enzalutamide monotherapy in hormone-naive prostate cancer:primary analysis of an open-label, single-arm, phase 2 study. Lancet Oncol 2014; 15:592-600; PMID:24739897; http://dx.doi.org/10.1016/S1470-2045(14)70129-9
113. F.L.Tarish, N.Schultz, A.Tanoglidi, H.Hamberg, H.Letocha, K.Karaszi, F.C.Hamdy, T.Granfors, T.Helleday. Castration radiosensitizes prostate cancer tissue by impairing DNA double-strand break repair. Sci Transl Med 2015; 7:312re11; PMID:26537259; http://dx.doi.org/10.1126/scitranslmed.aac5671
114. K.Yumimoto, K.I.Nakayama. Fbxw7 suppresses cancer metastasis by inhibiting niche formation. Oncoimmunology 2015; 4:e1022308; PMID:26405580; http://dx.doi.org/10.1080/2162402X.2015.1022308
115. K.Sakai, S.Kazama, Y.Nagai, K.Murono, T.Tanaka, S.Ishihara, E.Sunami, S.Tomida, K.Nishio, T.Watanabe. Chemoradiation provides a physiological selective pressure that increases the expansion of aberrant TP53 tumor variants in residual rectal cancerous regions. Oncotarget 2014; 5:9641-9; PMID:25275295; http://dx.doi.org/10.18632/oncotarget.2438
116. L.Wang, X.Ye, Y.Liu, W.Wei, Z.Wang. Aberrant regulation of FBW7 in cancer. Oncotarget 2014; 5:2000-15; PMID:24899581; http://dx.doi.org/10.18632/oncotarget.1859
117. J.M.Beckta, S.M.Dever, N.Gnawali, A.Khalil, A.Sule, S.E.Golding, E.Rosenberg, A.Narayanan, K.Kehn-Hall, B.Xu et al. Mutation of the BRCA1 SQ-cluster results in aberrant mitosis, reduced homologous recombination, and a compensatory increase in non-homologous end joining. Oncotarget 2015; 6:27674-87; PMID:26320175; http://dx.doi.org/10.18632/oncotarget.4876
118. Q.Zhang, D.Karnak, M.Tan, T.S.Lawrence, M.A.Morgan, Y.Sun. FBXW7 facilitates nonhomologous end-joining via K63-linked polyubiquitylation of XRCC4. Mol Cell 2016; 61:419-33; PMID:26774286; http://dx.doi.org/10.1016/j.molcel.2015.12.010
119. S.J.Dovedi, T.M.Illidge. The antitumor immune response generated by fractionated radiation therapy may be limited by tumor cell adaptive resistance and can be circumvented by PD-L1 blockade. Oncoimmunology 2015; 4:e1016709; PMID:26140246; http://dx.doi.org/10.1080/2162402X.2015.1016709
120. L.Huang, L.Li, H.Lemos, P.R.Chandler, G.Pacholczyk, B.Baban, G.N.Barber, Y.Hayakawa, T.L.McGaha, B.Ravishankar et al. Cutting edge:DNA sensing via the STING adaptor in myeloid dendritic cells induces potent tolerogenic responses. J Immunol 2013; 191:3509-13; PMID:23986532; http://dx.doi.org/10.4049/jimmunol.1301419
121. S.Liu, X.Cai, J.Wu, Q.Cong, X.Chen, T.Li, F.Du, J.Ren, Y.T.Wu, N.V.Grishin et al. Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation. Science 2015; 347:aaa2630; PMID:25636800; http://dx.doi.org/10.1126/science.aaa2630
122. L.Zitvogel, L.Galluzzi, O.Kepp, M.J.Smyth, G.Kroemer. Type I interferons in anticancer immunity. Nat Rev Immunol 2015; 15:405-14; PMID:26027717; http://dx.doi.org/10.1038/nri3845
123. L.Deng, H.Liang, B.Burnette, M.Beckett, T.Darga, R.R.Weichselbaum, Y.X.Fu. Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. J Clin Invest 2014; 124:687-95; PMID:24382348; http://dx.doi.org/10.1172/JCI67313
124. L.Deng, H.Liang, M.Xu, X.Yang, B.Burnette, A.Arina, X.D.Li, H.Mauceri, M.Beckett, T.Darga et al. STING-dependent cytosolic DNA Sensing promotes radiation-induced Type I interferon-dependent antitumor immunity in immunogenic tumors. Immunity 2014; 41:843-52; PMID:25517616; http://dx.doi.org/10.1016/j.immuni.2014.10.019
125. I.C.Salaroglio, I.Campia, J.Kopecka, E.Gazzano, S.Orecchia, D.Ghigo, C.Riganti. Zoledronic acid overcomes chemoresistance and immunosuppression of malignant mesothelioma. Oncotarget 2015; 6:1128-42; PMID:25544757; http://dx.doi.org/10.18632/oncotarget.2731
126. R.L.Bowman, J.A.Joyce. Therapeutic targeting of tumor-associated macrophages and microglia in glioblastoma. Immunotherapy 2014; 6:663-6; PMID:25041027; http://dx.doi.org/10.2217/imt.14.48
127. G.Comito, C.P.Segura, M.L.Taddei, M.Lanciotti, S.Serni, A.Morandi, P.Chiarugi, E.Giannoni. Zoledronic acid impairs stromal reactivity by inhibiting M2-macrophages polarization and prostate cancer-associated fibroblasts. Oncotarget 2016; PMID:27223431; http://dx.doi.org/10.18632/oncotarget.9497
128. Y.Hattori, K.Shibuya, K.Kojima, A.Miatmoko, K.Kawano, K.Ozaki, E.Yonemochi. Zoledronic acid enhances antitumor efficacy of liposomal doxorubicin. Int J Oncol 2015; 47:211-9; PMID:25955490; http://dx.doi.org/10.3892/ijo.2015.2991
129. C.Riganti, B.Castella, J.Kopecka, I.Campia, M.Coscia, G.Pescarmona, A.Bosia, D.Ghigo, M.Massaia. Zoledronic acid restores doxorubicin chemosensitivity and immunogenic cell death in multidrug-resistant human cancer cells. PLoS One 2013; 8:e60975; PMID:23593363; http://dx.doi.org/10.1371/journal.pone.0060975
130. J.W.Denham, D.Joseph, D.S.Lamb, N.A.Spry, G.Duchesne, J.Matthews, C.Atkinson, K.H.Tai, D.Christie, L.Kenny et al. Short-term androgen suppression and radiotherapy versus intermediate-term androgen suppression and radiotherapy, with or without zoledronic acid, in men with locally advanced prostate cancer (TROG 03.04 RADAR):an open-label, randomised, phase 3 factorial trial. Lancet Oncol 2014; 15:1076-89; PMID:25130995; http://dx.doi.org/10.1016/S1470-2045(14)70328-6
131. A.Hervieu, C.Rebe, F.Vegran, F.Chalmin, M.Bruchard, P.Vabres, L.Apetoh, F.Ghiringhelli, G.Mignot. Dacarbazine-mediated upregulation of NKG2D ligands on tumor cells activates NK and CD8 T cells and restrains melanoma growth. J Invest Dermatol 2013; 133:499-508; PMID:22951720; http://dx.doi.org/10.1038/jid.2012.273
132. A.Iannello, D.H.Raulet. Immunosurveillance of senescent cancer cells by natural killer cells. Oncoimmunology 2014; 3:e27616; PMID:24800169; http://dx.doi.org/10.4161/onci.27616
133. N.T.Joncker, D.H.Raulet. Regulation of NK cell responsiveness to achieve self-tolerance and maximal responses to diseased target cells. Immunol Rev 2008; 224:85-97; PMID:18759922; http://dx.doi.org/10.1111/j.1600-065X.2008.00658.x
134. D.H.Raulet, N.Guerra. Oncogenic stress sensed by the immune system:role of natural killer cell receptors. Nat Rev Immunol 2009; 9:568-80; PMID:19629084; http://dx.doi.org/10.1038/nri2604
135. M.G.Ruocco, K.A.Pilones, N.Kawashima, M.Cammer, J.Huang, J.S.Babb, M.Liu, S.C.Formenti, M.L.Dustin, S.Demaria. Suppressing T cell motility induced by anti-CTLA-4 monotherapy improves antitumor effects. J Clin Invest 2012; 122:3718-30; PMID:22945631; http://dx.doi.org/10.1172/JCI61931
136. P.Vantourout, C.Willcox, A.Turner, C.M.Swanson, Y.Haque, O.Sobolev, A.Grigoriadis, A.Tutt, A.Hayday. Immunological visibility:posttranscriptional regulation of human NKG2D ligands by the EGF receptor pathway. Sci Transl Med 2014; 6:231ra49; PMID:24718859; http://dx.doi.org/10.1126/scitranslmed.3007579
137. L.Surace, V.Lysenko, A.O.Fontana, V.Cecconi, H.Janssen, A.Bicvic, M.Okoniewski, M.Pruschy, R.Dummer, J.Neefjes et al. Complement is a central mediator of radiotherapy-induced tumor-specific immunity and clinical response. Immunity 2015; 42:767-77; PMID:25888260; http://dx.doi.org/10.1016/j.immuni.2015.03.009
138. C.Twyman-Saint Victor, A.J.Rech, A.Maity, R.Rengan, K.E.Pauken, E.Stelekati, J.L.Benci, B.Xu, H.Dada, P.M.Odorizzi et al. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature 2015; 520:373-7; PMID:25754329; http://dx.doi.org/10.1038/nature14292
139. E.B.Golden, A.Chhabra, A.Chachoua, S.Adams, M.Donach, M.Fenton-Kerimian, K.Friedman, F.Ponzo, J.S.Babb, J.Goldberg et al. Local radiotherapy and granulocyte-macrophage colony-stimulating factor to generate abscopal responses in patients with metastatic solid tumours:a proof-of-principle trial. Lancet Oncol 2015; 16:795-803; PMID:26095785; http://dx.doi.org/10.1016/S1470-2045(15)00054-6
140. J.Galon, B.Mlecnik, G.Bindea, H.K.Angell, A.Berger, C.Lagorce, A.Lugli, I.Zlobec, A.Hartmann, C.Bifulco et al. Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours. J Pathol 2014; 232:199-209; PMID:24122236; http://dx.doi.org/10.1002/path.4287
141. M.G.Anitei, G.Zeitoun, B.Mlecnik, F.Marliot, N.Haicheur, A.M.Todosi, A.Kirilovsky, C.Lagorce, G.Bindea, D.Ferariu et al. Prognostic and predictive values of the immunoscore in patients with rectal cancer. Clin Cancer Res 2014; 20:1891-9; PMID:24691640; http://dx.doi.org/10.1158/1078-0432.CCR-13-2830
142. B.P.Ceresa, J.L.Peterson. Cell and molecular biology of epidermal growth factor receptor. Int Rev Cell Mol Biol 2014; 313:145-78; PMID:25376492; http://dx.doi.org/10.1016/B978-0-12-800177-6.00005-0
143. E.Vacchelli, J.Pol, N.Bloy, A.Eggermont, I.Cremer, W.H.Fridman, J.Galon, A.Marabelle, H.Kohrt, L.Zitvogel et al. Trial Watch:Tumor-targeting monoclonal antibodies for oncological indications. Oncoimmunology 2015; 4:e985940; PMID:25949870; http://dx.doi.org/10.4161/2162402X.2014.985940
144. D.Cunningham, Y.Humblet, S.Siena, D.Khayat, H.Bleiberg, A.Santoro, D.Bets, M.Mueser, A.Harstrick, C.Verslype et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004; 351:337-45; PMID:15269313; http://dx.doi.org/10.1056/NEJMoa033025
145. T.de La Motte Rouge, L.Galluzzi, K.A.Olaussen, Y.Zermati, E.Tasdemir, T.Robert, H.Ripoche, V.Lazar, P.Dessen, F.Harper et al. A novel epidermal growth factor receptor inhibitor promotes apoptosis in non-small cell lung cancer cells resistant to erlotinib. Cancer Res 2007; 67:6253-62; PMID:17616683; http://dx.doi.org/10.1158/0008-5472.CAN-07-0538
146. F.Aranda, E.Vacchelli, A.Eggermont, J.Galon, W.H.Fridman, L.Zitvogel, G.Kroemer, L.Galluzzi. Trial Watch:immunostimulatory monoclonal antibodies in cancer therapy. Oncoimmunology 2014; 3:e27297; PMID:24701370; http://dx.doi.org/10.4161/onci.27297
147. J.J.Luke, P.A.Ott. PD-1 pathway inhibitors:the next generation of immunotherapy for advanced melanoma. Oncotarget 2015; 6:3479-92; PMID:25682878; http://dx.doi.org/10.18632/oncotarget.2980
148. M.Kortylewski, P.Swiderski, A.Herrmann, L.Wang, C.Kowolik, M.Kujawski, H.Lee, A.Scuto, Y.Liu, C.Yang et al. In vivo delivery of siRNA to immune cells by conjugation to a TLR9 agonist enhances antitumor immune responses. Nat Biotechnol 2009; 27:925-32; PMID:19749770; http://dx.doi.org/10.1038/nbt.1564
149. M.Kortylewski, Y.H.Kuo. Push and release:TLR9 activation plus STAT3 blockade for systemic antitumor immunity. Oncoimmunology 2014; 3:e27441; PMID:24800162; http://dx.doi.org/10.4161/onci.27441
150. D.Moreira, Q.Zhang, D.M.Hossain, S.Nechaev, H.Li, C.M.Kowolik, M.D'Apuzzo, S.Forman, J.Jones, S.K.Pal et al. TLR9 signaling through NF-kappaB/RELA and STAT3 promotes tumor-propagating potential of prostate cancer cells. Oncotarget 2015; 6:17302-13; PMID:26046794; http://dx.doi.org/10.18632/oncotarget.4029
151. E.B.Golden, A.Chachoua, M.Fenton-Kerimian, S.Demaria, S.C.Formenti. Abscopal responses in patients with refractory metastatic NSCLC treated with concurrent radiotherapy and CTLA-4 immune checkpoint blockade:evidence for the in situ vaccination hypothesis of radiotherapy. Cancer Research 2015; 75:S244; http://dx.doi.org/10.1158/1538-7445.AM2015-244
152. M.S.Khodadoust, M.P.Chu, D.Czerwinski, K.McDonald, S.Long, H.E.Kohrt, R.T.Hoppe, R.H.Advani, R.Lowsky, R.Levy. Phase I/II study of intratumoral injection of SD-101, an immunostimulatory CpG, and intratumoral injection of ipillumumab, an anti-CTLA-4 monoclonal antibody, in combination with local radiation in low-grade B-cell lymphomas. ASCO Annual Meeting, 2015
153. H.Wei, L.Zhao, I.Hellstrom, K.E.Hellstrom, Y.Guo. Dual targeting of CD137 co-stimulatory and PD-1 co-inhibitory molecules for ovarian cancer immunotherapy. Oncoimmunology 2014; 3:e28248; PMID:25050196; http://dx.doi.org/10.4161/onci.28248
154. C.Robert, G.V.Long, B.Brady, C.Dutriaux, M.Maio, L.Mortier, J.C.Hassel, P.Rutkowski, C.McNeil, E.Kalinka-Warzocha et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 2015; 372(4):2006-17; PMID:25399552; http://dx.doi.org/10.1056/NEJMoa1412082
155. S.M.Ansell, A.M.Lesokhin, I.Borrello, A.Halwani, E.C.Scott, M.Gutierrez, S.J.Schuster, M.M.Millenson, D.Cattry, G.J.Freeman et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med 2015; 372(4):311-9; PMID:25482239; http://dx.doi.org/10.1056/NEJMoa1411087
156. C.Robert, A.Ribas, J.D.Wolchok, F.S.Hodi, O.Hamid, R.Kefford, J.S.Weber, A.M.Joshua, W.J.Hwu, T.C.Gangadhar et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma:a randomised dose-comparison cohort of a phase 1 trial. Lancet 2014; 384:1109-17; PMID:25034862; http://dx.doi.org/10.1016/S0140-6736(14)60958-2
157. P.C.Tumeh, C.L.Harview, J.H.Yearley, I.P.Shintaku, E.J.Taylor, L.Robert, B.Chmielowski, M.Spasic, G.Henry, V.Ciobanu et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 2014; 515:568-71; PMID:25428505; http://dx.doi.org/10.1038/nature13954
158. E.B.Garon, N.A.Rizvi, R.Hui, N.Leighl, A.S.Balmanoukian, J.P.Eder, A.Patnaik, C.Aggarwal, M.Gubens, L.Horn et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 2015; 372:2018-28; PMID:25891174; http://dx.doi.org/10.1056/NEJMoa1501824
159. C.Robert, J.Schachter, G.V.Long, A.Arance, J.J.Grob, L.Mortier, A.Daud, M.S.Carlino, C.McNeil, M.Lotem et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 2015; 372:2521-32; PMID:25891173; http://dx.doi.org/10.1056/NEJMoa1503093
160. G.Kroemer, L.Galluzzi. Combinatorial immunotherapy with checkpoint blockers solves the problem of metastatic melanoma-An exclamation sign with a question mark. Oncoimmunology 2015; 4:e1058037; PMID:26140249; http://dx.doi.org/10.1080/2162402X.2015.1058037
161. N.H.Segal, N.E.Kemeny, A.Cercek, D.L.Reidy, P.J.Raasch, P.Warren, A.E.Hrabovsky, N.Campbell, J.Shia, K.A.Goodman et al. Non-randomized phase II study to assess the efficacy of pembrolizumab (Pem) plus radiotherapy (RT) or ablation in mismatch repair proficient (pMMR) metastatic colorectal cancer (mCRC) patients. ASCO Annual Meeting, 2016
162. D.T.Le, A.Wang-Gillam, V.Picozzi, T.F.Greten, T.Crocenzi, G.Springett, M.Morse, H.Zeh, D.Cohen, R.L.Fine et al. Safety and survival with GVAX pancreas prime and Listeria monocytogenes-expressing mesothelin (CRS-207) boost vaccines for metastatic pancreatic cancer. J Clin Oncol 2015; 33:1325-33; PMID:25584002; http://dx.doi.org/10.1200/JCO.2014.57.4244
163. V.Brower. New approaches tackle rising pancreatic cancer rates. J Natl Cancer Inst 2014; 106; PMID:25535299; http://dx.doi.org/10.1093/jnci/dju417
164. K.C.Soares, A.A.Rucki, A.A.Wu, K.Olino, Q.Xiao, Y.Chai, A.Wamwea, E.Bigelow, E.Lutz, L.Liu et al. PD-1/PD-L1 blockade together with vaccine therapy facilitates effector T-cell infiltration into pancreatic tumors. J Immunother 2015; 38:1-11; PMID:25415283; http://dx.doi.org/10.1097/CJI.0000000000000062
165. G.Kroemer, L.Galluzzi. Immunotherapy of hematological cancers:PD-1 blockade for the treatment of Hodgkin's lymphoma. Oncoimmunology 2015; 4:e1008853; PMID:26155425; http://dx.doi.org/10.1080/2162402X.2015.1008853
166. K.Palucka, J.Banchereau. SnapShot:cancer vaccines. Cell 2014; 157:516-e1; PMID:24725415; http://dx.doi.org/10.1016/j.cell.2014.03.044
167. K.Palucka, J.Banchereau. Cancer immunotherapy via dendritic cells. Nat Rev Cancer 2012; 12:265-77; PMID:22437871; http://dx.doi.org/10.1038/nrc3258
168. A.Kolstad, J.Olweus. “In situ” vaccination for systemic effects in follicular lymphoma. Oncoimmunology 2015; 4:e1014773; PMID:26140239; http://dx.doi.org/10.1080/2162402X.2015.1014773
169. K.F.Bol, C.G.Figdor, E.H.Aarntzen, M.E.Welzen, M.M.van Rossum, W.A.Blokx, M.W.van de Rakt, N.M.Scharenborg, A.J.de Boer, J.M.Pots et al. Intranodal vaccination with mRNA-optimized dendritic cells in metastatic melanoma patients. Oncoimmunology 2015; 4:e1019197; PMID:26405571; http://dx.doi.org/10.1080/2162402X.2015.1019197
170. H.Ueno, A.K.Palucka, J.Banchereau. The expanding family of dendritic cell subsets. Nat Biotechnol 2010; 28:813-5; PMID:20697407; http://dx.doi.org/10.1038/nbt0810-813
171. H.Ueno, E.Klechevsky, N.Schmitt, L.Ni, A.L.Flamar, S.Zurawski, G.Zurawski, K.Palucka, J.Banchereau, S.Oh. Targeting human dendritic cell subsets for improved vaccines. Semin Immunol 2011; 23:21-7; PMID:21277223; http://dx.doi.org/10.1016/j.smim.2011.01.004
172. L.Deng, H.Liang, B.Burnette, R.R.Weicheslbaum, Y.X.Fu. Radiation and anti-PD-L1 antibody combinatorial therapy induces T cell-mediated depletion of myeloid-derived suppressor cells and tumor regression. Oncoimmunology 2014; 3:e28499; PMID:25050217; http://dx.doi.org/10.4161/onci.28499
173. More Benefits for Checkpoint Inhibitors in NSCLC. Cancer Discov 2015; 5:OF2; PMID:26511141; http://dx.doi.org/10.1158/2159-8290.CD-NB2015-148
174. A.Chawla, A.V.Philips, G.Alatrash, E.Mittendorf. Immune checkpoints:a therapeutic target in triple negative breast cancer. Oncoimmunology 2014; 3:e28325; PMID:24843833; http://dx.doi.org/10.4161/onci.28325
175. E.B.Garon. Current perspectives in immunotherapy for non-small cell lung cancer. Semin Oncol 2015; 42 Suppl 2:S11-8; PMID:26477470; http://dx.doi.org/10.1053/j.seminoncol.2015.09.019
176. S.L.Scarpace. Metastatic squamous cell non-small-cell lung cancer (NSCLC):disrupting the drug treatment paradigm with immunotherapies. Drugs Context 2015; 4:212289; PMID:26576187; http://dx.doi.org/10.7573/dic.212289
177. B.Boyerinas, C.Jochems, M.Fantini, C.R.Heery, J.L.Gulley, K.Y.Tsang, J.Schlom. Antibody-dependent cellular cytotoxicity activity of a novel anti-PD-L1 antibody avelumab (MSB0010718C) on human tumor cells. Cancer Immunol Res 2015; 3:1148-57; PMID:26014098; http://dx.doi.org/10.1158/2326-6066.CIR-15-0059
178. J.M.Reichert. Antibodies to watch in 2016. MAbs 2016; 8:197-204; PMID:26651519; http://dx.doi.org/10.1080/19420862.2015.1125583
179. L.Robert, C.Harview, R.Emerson, X.Wang, S.Mok, B.Homet, B.Comin-Anduix, R.C.Koya, H.Robins, P.C.Tumeh et al. Distinct immunological mechanisms of CTLA-4 and PD-1 blockade revealed by analyzing TCR usage in blood lymphocytes. Oncoimmunology 2014; 3:e29244; PMID:25083336; http://dx.doi.org/10.4161/onci.29244
180. L.Calabro, M.Maio. Immune checkpoint blockade in malignant mesothelioma:a novel therapeutic strategy against a deadly disease? Oncoimmunology 2014; 3:e27482; PMID:24734215; http://dx.doi.org/10.4161/onci.27482
181. C.C.Zielinski. A phase I study of MEDI4736, NNT-PD-L1 antibody in patients with advanced solid tumors. Transl Lung Cancer Res 2014; 3:406-7; PMID:25806335; http://dx.doi.org/10.3978/j.issn.2218-6751.2014.08.07
182. R.Ibrahim, R.Stewart, A.Shalabi. PD-L1 blockade for cancer treatment:MEDI4736. Semin Oncol 2015; 42:474-83; PMID:25965366; http://dx.doi.org/10.1053/j.seminoncol.2015.02.007
183. S.M.Lee, L.Q.Chow. A new addition to the PD-1 checkpoint inhibitors for non-small cell lung cancer-the anti-PDL1 antibody-MEDI4736. Transl Lung Cancer Res 2014; 3:408-10; PMID:25806336; http://dx.doi.org/10.3978/j.issn.2218-6751.2014.11.10
184. B.C.Creelan. Update on immune checkpoint inhibitors in lung cancer. Cancer Control 2014; 21:80-9; PMID:24357746
185. K.P.Papadopoulos, M.R.Crittenden, M.L.Johnson, A.C.Lockhart, K.N.Moore, G.S.Falchook, S.Formenti, R.D.Carvajal, R.S.Leidner, A.Naing et al. A first-in-human study of REGN2810, a monoclonal, fully human antibody to programmed death-1 (PD-1), in combination with immunomodulators including hypofractionated radiotherapy (hfRT). ASCO Annual Meeting, 2016
186. L.Ruggeri, E.Urbani, P.Andre, A.Mancusi, A.Tosti, F.Topini, M.Blery, L.Animobono, F.Romagne, N.Wagtmann et al. Effects of anti-NKG2A antibody administration on leukemia and normal hematopoietic cells. Haematologica 2016; 101:626-33; PMID:26721894; http://dx.doi.org/10.3324/haematol.2015.135301
187. Y.Zhang, G.Lv, X.Lou, D.Peng, X.Qu, X.Yang, D.A.Ayana, H.Guo, Y.Jiang. NKG2A expression and impaired function of NK cells in patients with new onset of Graves' disease. Int Immunopharmacol 2015; 24:133-9; PMID:25281394; http://dx.doi.org/10.1016/j.intimp.2014.09.020
188. S.Demaria, K.A.Pilones, S.C.Formenti, M.L.Dustin. Exploiting the stress response to radiation to sensitize poorly immunogenic tumors to anti-CTLA-4 treatment. Oncoimmunology 2013; 2:e23127; PMID:23802063; http://dx.doi.org/10.4161/onci.23127
189. A.Prica, R.Buckstein. Myelodysplastic syndrome successfully treated with adalimumab. J Clin Oncol 2015; 33:e4-6; PMID:24567429; http://dx.doi.org/10.1200/JCO.2013.49.4948
190. L.Senovilla, E.Vacchelli, J.Galon, S.Adjemian, A.Eggermont, W.H.Fridman, C.Sautes-Fridman, Y.Ma, E.Tartour, L.Zitvogel et al. Trial Watch:prognostic and predictive value of the immune infiltrate in cancer. Oncoimmunology 2012; 1:1323-43; PMID:23243596; http://dx.doi.org/10.4161/onci.22009
191. L.Senovilla, F.Aranda, L.Galluzzi, G.Kroemer. Impact of myeloid cells on the efficacy of anticancer chemotherapy. Curr Opin Immunol 2014; 30C:24-31; PMID:24950501; http://dx.doi.org/10.1016/j.coi.2014.05.009
192. S.Banerjee, K.Halder, S.Ghosh, A.Bose, S.Majumdar. The combination of a novel immunomodulator with a regulatory T cell suppressing antibody (DTA-1) regress advanced stage B16F10 solid tumor by repolarizing tumor associated macrophages in situ. Oncoimmunology 2015; 4:e995559; PMID:25949923; http://dx.doi.org/10.1080/2162402X.2014.995559
193. M.A.Cannarile, C.H.Ries, S.Hoves, D.Ruttinger. Targeting tumor-associated macrophages in cancer therapy and understanding their complexity. Oncoimmunology 2014; 3:e955356; PMID:25941615; http://dx.doi.org/10.4161/21624011.2014.955356
194. H.Trachtman, F.C.Fervenza, D.S.Gipson, P.Heering, D.R.Jayne, H.Peters, S.Rota, G.Remuzzi, L.C.Rump, L.K.Sellin et al. A phase 1, single-dose study of fresolimumab, an anti-TGF-beta antibody, in treatment-resistant primary focal segmental glomerulosclerosis. Kidney Int 2011; 79:1236-43; PMID:21368745; http://dx.doi.org/10.1038/ki.2011.33
195. J.C.Morris, A.R.Tan, T.E.Olencki, G.I.Shapiro, B.J.Dezube, M.Reiss, F.J.Hsu, J.A.Berzofsky, D.P.Lawrence. Phase I study of GC1008 (fresolimumab):a human anti-transforming growth factor-beta (TGFbeta) monoclonal antibody in patients with advanced malignant melanoma or renal cell carcinoma. PLoS One 2014; 9:e90353; PMID:24618589; http://dx.doi.org/10.1371/journal.pone.0090353
196. A.A.Wu, V.Drake, H.S.Huang, S.Chiu, L.Zheng. Reprogramming the tumor microenvironment:tumor-induced immunosuppressive factors paralyze T cells. Oncoimmunology 2015; 4:e1016700; PMID:26140242; http://dx.doi.org/10.1080/2162402X.2015.1016700
197. X.Chen, L.M.Wakefield, J.J.Oppenheim. Synergistic antitumor effects of a TGFbeta inhibitor and cyclophosphamide. Oncoimmunology 2014; 3:e28247; PMID:25050195; http://dx.doi.org/10.4161/onci.28247
198. L.Z.He, N.Prostak, L.J.Thomas, L.Vitale, J.Weidlick, A.Crocker, C.D.Pilsmaker, S.M.Round, A.Tutt, M.J.Glennie et al. Agonist anti-human CD27 monoclonal antibody induces T cell activation and tumor immunity in human CD27-transgenic mice. J Immunol 2013; 191:4174-83; PMID:24026078; http://dx.doi.org/10.4049/jimmunol.1300409
199. L.J.Thomas, L.Z.He, H.Marsh, T.Keler. Targeting human CD27 with an agonist antibody stimulates T-cell activation and antitumor immunity. Oncoimmunology 2014; 3:e27255; PMID:24605266; http://dx.doi.org/10.4161/onci.27255
200. M.Ruf, H.Moch, P.Schraml. Interaction of tumor cells with infiltrating lymphocytes via CD70 and CD27 in clear cell renal cell carcinoma. Oncoimmunology 2015; 4:e1049805; PMID:26587319; http://dx.doi.org/10.1080/2162402X.2015.1049805
201. V.Ramakrishna, K.Sundarapandiyan, B.Zhao, M.Bylesjo, H.C.Marsh, T.Keler. Characterization of the human T cell response to in vitro CD27 costimulation with varlilumab. J Immunother Cancer 2015; 3:37; PMID:26500773; http://dx.doi.org/10.1186/s40425-015-0080-2
202. H.I.Cho, S.H.Jung, H.J.Sohn, E.Celis, T.G.Kim. An optimized peptide vaccine strategy capable of inducing multivalent CD8+ T cell responses with potent antitumor effects. Oncoimmunology 2015; 4:e1043504; PMID:26451316; http://dx.doi.org/10.1080/2162402X.2015.1043504
203. V.Rainone, C.Martelli, L.Ottobrini, M.Biasin, M.Borelli, G.Lucignani, D.Trabattoni, M.Clerici. Immunological characterization of whole tumour lysate-loaded dendritic cells for cancer immunotherapy. PLoS One 2016; 11:e0146622; PMID:26795765; http://dx.doi.org/10.1371/journal.pone.0146622
204. L.Galluzzi, I.Vitale, J.Michels, C.Brenner, G.Szabadkai, A.Harel-Bellan, M.Castedo, G.Kroemer. Systems biology of cisplatin resistance:past, present and future. Cell Death Dis 2014; 5:e1257; PMID:24874729; http://dx.doi.org/10.1038/cddis.2013.428
205. L.Galluzzi, L.Senovilla, I.Vitale, J.Michels, I.Martins, O.Kepp, M.Castedo, G.Kroemer. Molecular mechanisms of cisplatin resistance. Oncogene 2012; 31:1869-83; PMID:21892204; http://dx.doi.org/10.1038/onc.2011.384
206. L.Galluzzi, O.Kepp, M.G.Vander Heiden, G.Kroemer. Metabolic targets for cancer therapy. Nat Rev Drug Discov 2013; 12:829-46; PMID:24113830; http://dx.doi.org/10.1038/nrd4145
207. H.Yan, D.W.Parsons, G.Jin, R.McLendon, B.A.Rasheed, W.Yuan, I.Kos, I.Batinic-Haberle, S.Jones, G.J.Riggins et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med 2009; 360:765-73; PMID:19228619; http://dx.doi.org/10.1056/NEJMoa0808710
208. S.Zhao, Y.Lin, W.Xu, W.Jiang, Z.Zha, P.Wang, W.Yu, Z.Li, L.Gong, Y.Peng et al. Glioma-derived mutations in IDH1 dominantly inhibit IDH1 catalytic activity and induce HIF-1alpha. Science 2009; 324:261-5; PMID:19359588; http://dx.doi.org/10.1126/science.1170944
209. L.Galluzzi, E.Vacchelli, J.M.Bravo-San Pedro, A.Buque, L.Senovilla, E.E.Baracco, N.Bloy, F.Castoldi, J.P.Abastado, P.Agostinis et al. Classification of current anticancer immunotherapies. Oncotarget 2014; 5:12472-508; PMID:25537519; http://dx.doi.org/10.18632/oncotarget.2998
210. R.H.Andtbacka, H.L.Kaufman, F.Collichio, T.Amatruda, N.Senzer, J.Chesney, K.A.Delman, L.E.Spitler, I.Puzanov, S.S.Agarwala et al. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol 2015; 33:2780-8; PMID:26014293; http://dx.doi.org/10.1200/JCO.2014.58.3377
211. J.M.Markert, S.N.Razdan, H.C.Kuo, A.Cantor, A.Knoll, M.Karrasch, L.B.Nabors, M.Markiewicz, B.S.Agee, J.M.Coleman et al. A phase 1 trial of oncolytic HSV-1, G207, given in combination with radiation for recurrent GBM demonstrates safety and radiographic responses. Mol Ther 2014; 22:1048-55; PMID:24572293; http://dx.doi.org/10.1038/mt.2014.22
212. F.Aranda, E.Vacchelli, F.Obrist, A.Eggermont, J.Galon, W.Herve Fridman, I.Cremer, E.Tartour, L.Zitvogel, G.Kroemer et al. Trial Watch:adoptive cell transfer for anticancer immunotherapy. Oncoimmunology 2014; 3:e28344; PMID:25050207; http://dx.doi.org/10.4161/onci.28344
213. P.Matzner, L.Sorski, L.Shaashua, E.Elbaz, H.Lavon, R.Melamed, E.Rosenne, N.Gotlieb, A.Benbenishty, S.G.Reed et al. Perioperative treatment with the new synthetic TLR-4 agonist GLA-SE reduces cancer metastasis without adverse effects. Int J Cancer 2016; 138:1754-64; PMID:26453448; http://dx.doi.org/10.1002/ijc.29885
214. M.T.Orr, M.S.Duthie, H.P.Windish, E.A.Lucas, J.A.Guderian, T.E.Hudson, N.Shaverdian, J.O'Donnell, A.L.Desbien, S.G.Reed et al. MyD88 and TRIF synergistic interaction is required for TH1-cell polarization with a synthetic TLR4 agonist adjuvant. Eur J Immunol 2013; 43:2398-408; PMID:23716300; http://dx.doi.org/10.1002/eji.201243124
215. A.M.Krieg. Toll-like receptor 9 (TLR9) agonists in the treatment of cancer. Oncogene 2008; 27:161-7; PMID:18176597; http://dx.doi.org/10.1038/sj.onc.1210911
216. M.Mella, J.H.Kauppila, P.Karihtala, P.Lehenkari, A.Jukkola-Vuorinen, Y.Soini, P.Auvinen, M.H.Vaarala, H.Ronkainen, S.Kauppila et al. Tumor infiltrating CD8+ T lymphocyte count is independent of tumor TLR9 status in treatment naive triple negative breast cancer and renal cell carcinoma. Oncoimmunology 2015; 4:e1002726; PMID:26155410; http://dx.doi.org/10.1080/2162402X.2014.1002726
217. M.van Seters, M.van Beurden, F.J.ten Kate, I.Beckmann, P.C.Ewing, M.J.Eijkemans, M.J.Kagie, C.J.Meijer, N.K.Aaronson, A.Kleinjan et al. Treatment of vulvar intraepithelial neoplasia with topical imiquimod. N Engl J Med 2008; 358:1465-73; PMID:18385498; http://dx.doi.org/10.1056/NEJMoa072685
218. L.Henriques, M.Palumbo, M.P.Guay, B.Bahoric, M.Basik, P.Kavan, G.Batist. Imiquimod in the treatment of breast cancer skin metastasis. J Clin Oncol 2014; 32:e22-5; PMID:24419128; http://dx.doi.org/10.1200/JCO.2012.46.4883
219. E.C.Smyth, M.Flavin, M.P.Pulitzer, G.J.Gardner, P.D.Costantino, D.S.Chi, K.Bogatch, P.B.Chapman, J.D.Wolchok, G.K.Schwartz et al. Treatment of locally recurrent mucosal melanoma with topical imiquimod. J Clin Oncol 2011; 29:e809-11; PMID:22010009; http://dx.doi.org/10.1200/JCO.2011.36.8829
220. M.Z.Dewan, C.Vanpouille-Box, N.Kawashima, S.DiNapoli, J.S.Babb, S.C.Formenti, S.Adams, S.Demaria. Synergy of topical toll-like receptor 7 agonist with radiation and low-dose cyclophosphamide in a mouse model of cutaneous breast cancer. Clin Cancer Res 2012; 18:6668-78; PMID:23048078; http://dx.doi.org/10.1158/1078-0432.CCR-12-0984
221. S.Demaria, C.Vanpouille-Box, S.C.Formenti, S.Adams. The TLR7 agonist imiquimod as an adjuvant for radiotherapy-elicited in situ vaccination against breast cancer. Oncoimmunology 2013; 2:e25997; PMID:24404422; http://dx.doi.org/10.4161/onci.25997
222. E.Garaci, F.Pica, C.Matteucci, R.Gaziano, C.D'Agostini, M.T.Miele, R.Camerini, A.T.Palamara, C.Favalli, A.Mastino et al. Historical review on thymosin alpha1 in oncology:preclinical and clinical experiences. Expert Opin Biol Ther 2015; 15 Suppl 1:S31-9; PMID:26096345; http://dx.doi.org/10.1517/14712598.2015.1017466
223. R.De Sanctis, A.Marrari, A.Santoro. Trabectedin for the treatment of soft tissue sarcomas. Expert Opin Pharmacother 2016; 17(11):1569-77; PMID:27328277; http://dx.doi.org/10.1080/14656566.2016.1204295
224. E.M.Gordon, K.K.Sankhala, N.Chawla, S.P.Chawla. Trabectedin for soft tissue sarcoma:current status and future perspectives. Adv Ther 2016; 33(7):1055-71; PMID:27234989; http://dx.doi.org/10.1007/s12325-016-0344-3
225. A.Kawai, N.Araki, H.Sugiura, T.Ueda, T.Yonemoto, M.Takahashi, H.Morioka, H.Hiraga, T.Hiruma, T.Kunisada et al. Trabectedin monotherapy after standard chemotherapy versus best supportive care in patients with advanced, translocation-related sarcoma:a randomised, open-label, phase 2 study. Lancet Oncol 2015; 16:406-16; PMID:25795406; http://dx.doi.org/10.1016/S1470-2045(15)70098-7
226. X.H.Jia, Y.Du, D.Mao, Z.L.Wang, Z.Q.He, J.D.Qiu, X.B.Ma, W.T.Shang, D.Ding, J.Tian. Zoledronic acid prevents the tumor-promoting effects of mesenchymal stem cells via MCP-1 dependent recruitment of macrophages. Oncotarget 2015; 6:26018-28; PMID:26305552; http://dx.doi.org/10.18632/oncotarget.4658
227. M.H.Andersen, I.M.Svane. Indoleamine 2,3-dioxygenase vaccination. Oncoimmunology 2015; 4:e983770; PMID:25949864; http://dx.doi.org/10.4161/2162402X.2014.983770
228. S.Y.Park, M.J.Kim, S.A.Park, J.S.Kim, K.N.Min, D.K.Kim, W.Lim, J.S.Nam, Y.Y.Sheen. Combinatorial TGF-beta attenuation with paclitaxel inhibits the epithelial-to-mesenchymal transition and breast cancer stem-like cells. Oncotarget 2015; 6:37526-43; PMID:26462028; http://dx.doi.org/10.18632/oncotarget.6063
229. C.Y.Park, K.N.Min, J.Y.Son, S.Y.Park, J.S.Nam, D.K.Kim, Y.Y.Sheen. An novel inhibitor of TGF-beta type I receptor, IN-1130, blocks breast cancer lung metastasis through inhibition of epithelial-mesenchymal transition. Cancer Lett 2014; 351:72-80; PMID:24887560; http://dx.doi.org/10.1016/j.canlet.2014.05.006
230. J.L.Adams, J.Smothers, R.Srinivasan, A.Hoos. Big opportunities for small molecules in immuno-oncology. Nat Rev Drug Discov 2015; 14:603-22; PMID:26228631; http://dx.doi.org/10.1038/nrd4596
231. Z.L.Li, S.B.Ye, L.Y.OuYang, H.Zhang, Y.S.Chen, J.He, Q.Y.Chen, C.N.Qian, X.S.Zhang, J.Cui et al. COX-2 promotes metastasis in nasopharyngeal carcinoma by mediating interactions between cancer cells and myeloid-derived suppressor cells. Oncoimmunology 2015; 4:e1044712; PMID:26451317; http://dx.doi.org/10.1080/2162402X.2015.1044712
232. A.Buque, N.Bloy, F.Aranda, I.Cremer, A.Eggermont, W.H.Fridman, J.Fucikova, J.Galon, R.Spisek, E.Tartour et al. Trial Watch:small molecules targeting the immunological tumor microenvironment for cancer therapy. Oncoimmunology 2016; 5(6):e1149674; PMID:27471617; http://dx.doi.org/10.1080/2162402X.2016.1149674
233. S.Bieri, C.Helg, B.Chapuis, R.Miralbell. Total body irradiation before allogeneic bone marrow transplantation:is more dose better? Int J Radiat Oncol Biol Phys 2001; 49:1071-7; PMID:11240249; http://dx.doi.org/10.1016/S0360-3016(00)01491-7
234. A.Derer, B.Frey, R.Fietkau, U.S.Gaipl. Immune-modulating properties of ionizing radiation:rationale for the treatment of cancer by combination radiotherapy and immune checkpoint inhibitors. Cancer Immunol Immunother 2016; 65:779-86; PMID:26590829; http://dx.doi.org/10.1007/s00262-015-1771-8
235. D.V.Krysko, P.Agostinis, O.Krysko, A.D.Garg, C.Bachert, B.N.Lambrecht, P.Vandenabeele. Emerging role of damage-associated molecular patterns derived from mitochondria in inflammation. Trends Immunol 2011; 32:157-64; PMID:21334975; http://dx.doi.org/10.1016/j.it.2011.01.005
236. R.E.Vatner, B.T.Cooper, C.Vanpouille-Box, S.Demaria, S.C.Formenti. Combinations of immunotherapy and radiation in cancer therapy. Front Oncol 2014; 4:325; PMID:25506582; http://dx.doi.org/10.3389/fonc.2014.00325
237. S.Demaria, E.B.Golden, S.C.Formenti. Role of local radiation therapy in cancer immunotherapy. JAMA Oncol 2015; 1:1325-32; PMID:26270858; http://dx.doi.org/10.1001/jamaoncol.2015.2756
238. C.I.Vanpouille-Box, M.Aryankalayil, K.A.Pilones, S.C.Formenti, N.Coleman, S.Demaria. Fractionated but not single dose radiation is an optimal adjuvant for in situ tumor vaccination. Cancer Res 2015; 75:S2493; http://dx.doi.org/10.1158/1538-7445.AM2015-2493
239. S.Gay, M.Foiani. Nuclear envelope and chromatin, lock and key of genome integrity. Int Rev Cell Mol Biol 2015; 317:267-330; PMID:26008788; http://dx.doi.org/10.1016/bs.ircmb.2015.03.001
240. J.M.Nicholson, D.Cimini. Link between aneuploidy and chromosome instability. Int Rev Cell Mol Biol 2015; 315:299-317; PMID:25708466; http://dx.doi.org/10.1016/bs.ircmb.2014.11.002
241. L.Zitvogel, L.Galluzzi, M.J.Smyth, G.Kroemer. Mechanism of action of conventional and targeted anticancer therapies:reinstating immunosurveillance. Immunity 2013; 39:74-88; PMID:23890065; http://dx.doi.org/10.1016/j.immuni.2013.06.014