Immune modulation of the tumor microenvironment for enhancing cancer immunotherapy

OncoImmunology

Volumn 2, Issue 8, 2013, Pages

  Devaud, Christel ^a   John, Liza B ^a   Westwood, Jennifer A ^a   Darcy, Phillip K ^a,b   Kershaw, Michael H ^a,b  

^a UNIVERSITY OF MELBOURNE   (Australia)

^b MONASH UNIVERSITY   (Australia)

Author keywords

Immunosuppression; Immunotherapy; Macrophages; Regulatory T cells; Tumor microenvironment

Indexed keywords

1 METHYL TRYPTOPHAN; ALPHA CD137 ANTIGEN; ALPHA CD40 ANTIBODY; ALPHA INTERFERON; ALPHA INTERLEUKIN 10 MONOCLONAL ANTIBODY; CANCER ANTIBODY; CANCER VACCINE; CCL1 ANTIBODY; CCL16 CHEMOKINE; CD137 ANTIBODY; CD40 ANTIBODY; CD40 LIGAND; CHEMOKINE; DENDRITIC CELL VACCINE; DISIALOGANGLIOSIDE ANTIBODY; DNA VACCINE; GP100 VACCINE; INDOLEAMINE 2,3 DIOXYGENASE INHIBITOR; INTERLEUKIN 12; IPILIMUMAB; MONOCLONAL ANTIBODY; ONCOLYTIC VIRUS; OVALBUMIN; POLYINOSINIC POLYCYTIDYLIC ACID; PROSTAGLANDIN SYNTHASE INHIBITOR; RETINOIC ACID; SECONDARY LYMPHOID TISSUE CHEMOKINE; TUMOR ANTIGEN; UNCLASSIFIED DRUG; UNINDEXED DRUG; VASCULOTROPIN ANTIBODY;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER IMMUNOTHERAPY; CANCER SURVIVAL; CELL THERAPY; CLINICAL EFFECTIVENESS; CPG ISLAND; DISTANT METASTASIS; DRUG EFFICACY; DRUG MECHANISM; DRUG TARGETING; HUMAN; IMMUNE RESPONSE; IMMUNOMODULATION; LYMPHOCYTE DEPLETION; LYMPHOCYTE DIFFERENTIATION; MELANOMA; NONHUMAN; NUCLEAR REPROGRAMMING; OVERALL SURVIVAL; PRIMARY TUMOR; PROTEIN DETERMINATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; REGULATORY T LYMPHOCYTE; SIGNAL TRANSDUCTION; SURVIVAL RATE; TARGET CELL DESTRUCTION; TUMOR CELL DESTRUCTION; TUMOR MICROENVIRONMENT; VIRAL GENE DELIVERY SYSTEM;

EID: 84885757630     PISSN: 21624011     EISSN: 2162402X     Source Type: Journal    
DOI: 10.4161/onci.25961     Document Type: Article

References (97)

1. Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010; 363:711-23; PMID:20525992; http://dx.doi.org/10.1056/ NEJMoa1003466
2. Salles G, Seymour JF, Offner F, López-Guillermo A, Belada D, Xerri L, Feugier P, Bouabdallah R, Catalano JV, Brice P, et al. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet 2011; 377:42-51; PMID:21176949; http://dx.doi.org/10.1016/ S0140-6736(10)62175-7
3. Dudley ME, Yang JC, Sherry R, Hughes MS, Royal R, Kammula U, Robbins PF, Huang J, Citrin DE, Leitman SF, et al. Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J Clin Oncol 2008; 26:5233-9; PMID:18809613; http://dx.doi.org/10.1200/JCO.2008.16.5449
4. Liotta LA, Kohn EC. The microenvironment of the tumour-host interface. Nature 2001; 411:375-9; PMID:11357145; http://dx.doi. org/10.1038/35077241
5. Marigo I, Dolcetti L, Serafini P, Zanovello P, Bronte V. Tumor-induced tolerance and immune suppression by myeloid derived suppressor cells. Immunol Rev 2008; 222:162-79; PMID:18364001; http://dx.doi. org/10.1111/j.1600-065X.2008.00602.x
6. Shevach EM. Mechanisms of foxp3+ T regulatory cell-mediated suppression. Immunity 2009; 30:636-45; PMID:19464986; http://dx.doi.org/10.1016/j. immuni.2009.04.010
7. Sica A, Larghi P, Mancino A, Rubino L, Porta C, Totaro MG, Rimoldi M, Biswas SK, Allavena P, Mantovani A. Macrophage polarization in tumour progression. Semin Cancer Biol 2008; 18:349-55; PMID:18467122; http://dx.doi.org/10.1016/j. semcancer.2008.03.004
8. Groh V, Wu J, Yee C, Spies T. Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation. Nature 2002; 419:734-8; PMID:12384702; http://dx.doi.org/10.1038/ nature01112
9. Smyth MJ, Cretney E, Kershaw MH, Hayakawa Y. Cytokines in cancer immunity and immunotherapy. Immunol Rev 2004; 202:275-93; PMID:15546400; http://dx.doi.org/10.1111/j.0105-2896.2004.00199.x
10. Aruga A, Aruga E, Tanigawa K, Bishop DK, Sondak VK, Chang AE. Type 1 versus type 2 cytokine release by Vbeta T cell subpopulations determines in vivo antitumor reactivity: IL-10 mediates a suppressive role. J Immunol 1997; 159:664-73; PMID:9218581
11. Rubinstein N, Alvarez M, Zwirner NW, Toscano MA, Ilarregui JM, Bravo A, Mordoh J, Fainboim L, Podhajcer OL, Rabinovich GA. Targeted inhibition of galectin-1 gene expression in tumor cells results in heightened T cell-mediated rejection; A potential mechanism of tumor-immune privilege. Cancer Cell 2004; 5:241-51; PMID:15050916; http://dx.doi. org/10.1016/S1535-6108(04)00024-8
12. Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, Roche PC, Lu J, Zhu G, Tamada K, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 2002; 8:793-800; PMID:12091876; http:// dx.doi.org/10.1038/nm0902-1039c
13. Brahmer JR, Drake CG, Wollner I, Powderly JD, Picus J, Sharfman WH, Stankevich E, Pons A, Salay TM, McMiller TL, et al. Phase I study of singleagent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol 2010; 28:3167-75; PMID:20516446; http://dx.doi.org/10.1200/JCO.2009.26.7609
14. Phan GQ, Yang JC, Sherry RM, Hwu P, Topalian SL, Schwartzentruber DJ, Restifo NP, Haworth LR, Seipp CA, Freezer LJ, et al. Cancer regression and autoimmunity induced by cytotoxic T lymphocyteassociated antigen 4 blockade in patients with metastatic melanoma. Proc Natl Acad Sci U S A 2003; 100:8372-7; PMID:12826605; http://dx.doi. org/10.1073/pnas.1533209100
15. Peng W, Liu C, Xu C, Lou Y, Chen J, Yang Y, Yagita H, Overwijk WW, Lizée G, Radvanyi L, et al. PD-1 blockade enhances T-cell migration to tumors by elevating IFN-g inducible chemokines. Cancer Res 2012; 72:5209-18; PMID:22915761; http://dx.doi. org/10.1158/0008-5472.CAN-12-1187
16. Li B, VanRoey M, Wang C, Chen TH, Korman A, Jooss K. Anti-programmed death-1 synergizes with granulocyte macrophage colony-stimulating factor--secreting tumor cell immunotherapy providing therapeutic benefit to mice with established tumors. Clin Cancer Res 2009; 15:1623-34; PMID:19208793; http://dx.doi.org/10.1158/1078-0432.CCR-08-1825
17. Verbrugge I, Hagekyriakou J, Sharp LL, Galli M, West A, McLaughlin NM, Duret H, Yagita H, Johnstone RW, Smyth MJ, et al. Radiotherapy increases the permissiveness of established mammary tumors to rejection by immunomodulatory antibodies. Cancer Res 2012; 72:3163-74; PMID:22570253; http:// dx.doi.org/10.1158/0008-5472.CAN-12-0210
18. Curran MA, Montalvo W, Yagita H, Allison JP. PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc Natl Acad Sci U S A 2010; 107:4275-80; PMID:20160101; http://dx.doi.org/10.1073/pnas.0915174107
19. Lee MJ, Woo MY, Heo YM, Kim JS, Kwon MH, Kim K, Park S. The inhibition of the T-cell immunoglobulin and mucin domain 3 (Tim3) pathway enhances the efficacy of tumor vaccine. Biochem Biophys Res Commun 2010; 402:88-93; PMID:20920468; http://dx.doi.org/10.1016/j. bbrc.2010.09.121
20. Yu P, Steel JC, Zhang M, Morris JC, Waldmann TA. Simultaneous blockade of multiple immune system inhibitory checkpoints enhances antitumor activity mediated by interleukin-15 in a murine metastatic colon carcinoma model. Clin Cancer Res 2010; 16:6019-28; PMID:20924130; http://dx.doi. org/10.1158/1078-0432.CCR-10-1966
21. Ngiow SF, von Scheidt B, Akiba H, Yagita H, Teng MW, Smyth MJ. Anti-TIM3 antibody promotes T cell IFN-g-mediated antitumor immunity and suppresses established tumors. Cancer Res 2011; 71:3540-51; PMID:21430066; http://dx.doi. org/10.1158/0008-5472.CAN-11-0096
22. Pilon-Thomas S, Mackay A, Vohra N, Mulé JJ. Blockade of programmed death ligand 1 enhances the therapeutic efficacy of combination immunotherapy against melanoma. J Immunol 2010; 184:3442-9; PMID:20194714; http://dx.doi.org/10.4049/ jimmunol.0904114
23. Ohta A, Gorelik E, Prasad SJ, Ronchese F, Lukashev D, Wong MK, Huang X, Caldwell S, Liu K, Smith P, et al. A2A adenosine receptor protects tumors from antitumor T cells. Proc Natl Acad Sci U S A 2006; 103:13132-7; PMID:16916931; http://dx.doi. org/10.1073/pnas.0605251103
24. Jin D, Fan J, Wang L, Thompson LF, Liu A, Daniel BJ, Shin T, Curiel TJ, Zhang B. CD73 on tumor cells impairs antitumor T-cell responses: a novel mechanism of tumor-induced immune suppression. Cancer Res 2010; 70:2245-55; PMID:20179192; http://dx.doi.org/10.1158/0008-5472.CAN-09-3109
25. Wang L, Fan J, Thompson LF, Zhang Y, Shin T, Curiel TJ, Zhang B. CD73 has distinct roles in nonhematopoietic and hematopoietic cells to promote tumor growth in mice. J Clin Invest 2011; 121:2371-82; PMID:21537079; http://dx.doi.org/10.1172/ JCI45559
26. Sinha P, Clements VK, Fulton AM, Ostrand-Rosenberg S. Prostaglandin E2 promotes tumor progression by inducing myeloid-derived suppressor cells. Cancer Res 2007; 67:4507-13; PMID:17483367; http://dx.doi.org/10.1158/0008-5472.CAN-06-4174
27. Veltman JD, Lambers ME, van Nimwegen M, Hendriks RW, Hoogsteden HC, Aerts JG, Hegmans JP. COX-2 inhibition improves immunotherapy and is associated with decreased numbers of myeloid-derived suppressor cells in mesothelioma. Celecoxib influences MDSC function. BMC Cancer 2010; 10:464; PMID:20804550; http://dx.doi. org/10.1186/1471-2407-10-464
28. Kusmartsev S, Cheng F, Yu B, Nefedova Y, Sotomayor E, Lush R, Gabrilovich D. All-trans-retinoic acid eliminates immature myeloid cells from tumorbearing mice and improves the effect of vaccination. Cancer Res 2003; 63:4441-9; PMID:12907617
29. Hoelzinger DB, Smith SE, Mirza N, Dominguez AL, Manrique SZ, Lustgarten J. Blockade of CCL1 inhibits T regulatory cell suppressive function enhancing tumor immunity without affecting T effector responses. J Immunol 2010; 184:6833-42; PMID:20483762; http://dx.doi.org/10.4049/ jimmunol.0904084
30. Fridlender ZG, Buchlis G, Kapoor V, Cheng G, Sun J, Singhal S, Crisanti MC, Wang LC, Heitjan D, Snyder LA, et al. CCL2 blockade augments cancer immunotherapy. Cancer Res 2010; 70:109-18; PMID:20028856; http://dx.doi.org/10.1158/0008-5472.CAN-09-2326
31. Molon B, Ugel S, Del Pozzo F, Soldani C, Zilio S, Avella D, De Palma A, Mauri P, Monegal A, Rescigno M, et al. Chemokine nitration prevents intratumoral infiltration of antigen-specific T cells. J Exp Med 2011; 208:1949-62; PMID:21930770; http://dx.doi. org/10.1084/jem.20101956
32. Pere H, Montier Y, Bayry J, Quintin-Colonna F, Merillon N, Dransart E, Badoual C, Gey A, Ravel P, Marcheteau E, et al. A CCR4 antagonist combined with vaccines induces antigen-specific CD8+ T cells and tumor immunity against self antigens. Blood 2011; 118:4853-62; PMID:21908423; http://dx.doi. org/10.1182/blood-2011-01-329656
33. Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 2009; 9:162-74; PMID:19197294; http://dx.doi.org/10.1038/nri2506
34. Munn DH. Blocking IDO activity to enhance antitumor immunity. Front Biosci (Elite Ed) 2012; 4:734-45; PMID:22201909
35. Gough MJ, Killeen N, Weinberg AD. Targeting macrophages in the tumour environment to enhance the efficacy of aOX40 therapy. Immunology 2012; 136:437-47; PMID:22578109; http://dx.doi. org/10.1111/j.1365-2567.2012.03600.x
36. De Santo C, Serafini P, Marigo I, Dolcetti L, Bolla M, Del Soldato P, Melani C, Guiducci C, Colombo MP, Iezzi M, et al. Nitroaspirin corrects immune dysfunction in tumor-bearing hosts and promotes tumor eradication by cancer vaccination. Proc Natl Acad Sci U S A 2005; 102:4185-90; PMID:15753302; http://dx.doi.org/10.1073/pnas.0409783102
37. Serafini P, Meckel K, Kelso M, Noonan K, Califano J, Koch W, Dolcetti L, Bronte V, Borrello I. Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived suppressor cell function. J Exp Med 2006; 203:2691-702; PMID:17101732; http://dx.doi.org/10.1084/ jem.20061104
38. Ou X, Cai S, Liu P, Zeng J, He Y, Wu X, Du J. Enhancement of dendritic cell-tumor fusion vaccine potency by indoleamine-pyrrole 2,3-dioxygenase inhibitor, 1-MT. J Cancer Res Clin Oncol 2008; 134:525-33; PMID:17909857; http://dx.doi. org/10.1007/s00432-007-0315-9
39. Zeng J, Cai S, Yi Y, He Y, Wang Z, Jiang G, Li X, Du J. Prevention of spontaneous tumor development in a ret transgenic mouse model by ret peptide vaccination with indoleamine 2,3-dioxygenase inhibitor 1-methyl tryptophan. Cancer Res 2009; 69:3963-70; PMID:19383920; http://dx.doi.org/10.1158/0008-5472.CAN-08-2476
40. Yi YM, Zhang G, Zeng J, Huang SC, Li LL, Fang R, Jiang GM, Bu XZ, Cai SH, Du J. A new tumor vaccine: FAPt-MT elicits effective antitumor response by targeting indolamine2,3-dioxygenase in antigen presenting cells. Cancer Biol Ther 2011; 11:866-73; PMID:21372637; http://dx.doi. org/10.4161/cbt.11.10.15179
41. Gu T, Rowswell-Turner RB, Kilinc MO, Egilmez NK. Central role of IFNgamma-indoleamine 2,3-dioxygenase axis in regulation of interleukin-12-mediated antitumor immunity. Cancer Res 2010; 70:129-38; PMID:20028855; http://dx.doi. org/10.1158/0008-5472.CAN-09-3170
42. Gasparri AM, Jachetti E, Colombo B, Sacchi A, Curnis F, Rizzardi GP, Traversari C, Bellone M, Corti A. Critical role of indoleamine 2,3-dioxygenase in tumor resistance to repeated treatments with targeted IFNgamma. Mol Cancer Ther 2008; 7:3859-66; PMID:19074858; http://dx.doi.org/10.1158/1535-7163.MCT-08-0538
43. Zheng X, Koropatnick J, Chen D, Velenosi T, Ling H, Zhang X, Jiang N, Navarro B, Ichim TE, Urquhart B, et al. Silencing IDO in dendritic cells: a novel approach to enhance cancer immunotherapy in a murine breast cancer model. Int J Cancer 2013; 132:967-77; PMID:22870862; http://dx.doi. org/10.1002/ijc.27710
44. Yen MC, Lin CC, Chen YL, Huang SS, Yang HJ, Chang CP, Lei HY, Lai MD. A novel cancer therapy by skin delivery of indoleamine 2,3-dioxygenase siRNA. Clin Cancer Res 2009; 15:641-9; PMID:19147770; http://dx.doi.org/10.1158/1078-0432.CCR-08-1988
45. Zeisberger SM, Odermatt B, Marty C, Zehnder-Fjällman AH, Ballmer-Hofer K, Schwendener RA. Clodronate-liposome-mediated depletion of tumourassociated macrophages: a new and highly effective antiangiogenic therapy approach. Br J Cancer 2006; 95:272-81; PMID:16832418; http://dx.doi. org/10.1038/sj.bjc.6603240
46. Westwood JA, Haynes NM, Sharkey J, McLaughlin N, Pegram HJ, Schwendener RA, Smyth MJ, Darcy PK, Kershaw MH. Toll-Like Receptor Triggering and T-Cell Costimulation Induce Potent Antitumor Immunity in Mice. Clin Cancer Res 2009; 15:7624-33; PMID:19996209; http://dx.doi. org/10.1158/1078-0432.CCR-09-2201
47. Morales JK, Kmieciak M, Graham L, Feldmesser M, Bear HD, Manjili MH. Adoptive transfer of HER2/ neu-specific T cells expanded with alternating gamma chain cytokines mediate tumor regression when combined with the depletion of myeloid-derived suppressor cells. Cancer Immunol Immunother 2009; 58:941-53; PMID:18979098; http://dx.doi. org/10.1007/s00262-008-0609-z
48. Srivastava MK, Zhu L, Harris-White M, Kar UK, Huang M, Johnson MF, Lee JM, Elashoff D, Strieter R, Dubinett S, et al. Myeloid suppressor cell depletion augments antitumor activity in lung cancer. PLoS One 2012; 7:e40677; PMID:22815789; http:// dx.doi.org/10.1371/journal.pone.0040677
49. Shojaei F, Wu X, Malik AK, Zhong C, Baldwin ME, Schanz S, Fuh G, Gerber HP, Ferrara N. Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells. Nat Biotechnol 2007; 25:911-20; PMID:17664940; http://dx.doi. org/10.1038/nbt1323
50. Welford AF, Biziato D, Coffelt SB, Nucera S, Fisher M, Pucci F, Di Serio C, Naldini L, De Palma M, Tozer GM, et al. TIE2-expressing macrophages limit the therapeutic efficacy of the vascular-disrupting agent combretastatin A4 phosphate in mice. J Clin Invest 2011; 121:1969-73; PMID:21490397; http:// dx.doi.org/10.1172/JCI44562
51. Kudo-Saito C, Schlom J, Camphausen K, Coleman CN, Hodge JW. The requirement of multimodal therapy (vaccine, local tumor radiation, and reduction of suppressor cells) to eliminate established tumors. Clin Cancer Res 2005; 11:4533-44; PMID:15958639; http://dx.doi.org/10.1158/1078-0432.CCR-04-2237
52. Li J, Hu P, Khawli LA, Epstein AL. Complete regression of experimental solid tumors by combination LEC/chTNT-3 immunotherapy and CD25(+) T-cell depletion. Cancer Res 2003; 63:8384-92; PMID:14679000
53. Mandl SJ, Rountree RB, Dalpozzo K, Do L, Lombardo JR, Schoonmaker PL, Dirmeier U, Steigerwald R, Giffon T, Laus R, et al. Immunotherapy with MVABN ®-HER2 induces HER-2-specific Th1 immunity and alters the intratumoral balance of effector and regulatory T cells. Cancer Immunol Immunother 2012; 61:19-29; PMID:21822917; http://dx.doi. org/10.1007/s00262-011-1077-4
54. Klages K, Mayer CT, Lahl K, Loddenkemper C, Teng MW, Ngiow SF, Smyth MJ, Hamann A, Huehn J, Sparwasser T. Selective depletion of Foxp3+ regulatory T cells improves effective therapeutic vaccination against established melanoma. Cancer Res 2010; 70:7788-99; PMID:20924102; http:// dx.doi.org/10.1158/0008-5472.CAN-10-1736
55. Mattarollo SR, Steegh K, Li M, Duret H, Foong Ngiow S, Smyth MJ. Transient Foxp3(+) regulatory T-cell depletion enhances therapeutic anticancer vaccination targeting the immune-stimulatory properties of NKT cells. Immunol Cell Biol 2013; 91:105-14; PMID:23090488; http://dx.doi. org/10.1038/icb.2012.58
56. Guiducci C, Vicari AP, Sangaletti S, Trinchieri G, Colombo MP. Redirecting in vivo elicited tumor infiltrating macrophages and dendritic cells towards tumor rejection. Cancer Res 2005; 65:3437-46; PMID:15833879
57. Buhtoiarov IN, Sondel PM, Wigginton JM, Buhtoiarova TN, Yanke EM, Mahvi DA, Rakhmilevich AL. Anti-tumour synergy of cytotoxic chemotherapy and anti-CD40 plus CpGODN immunotherapy through repolarization of tumour-associated macrophages. Immunology 2011; 132:226-39; PMID:21039467; http://dx.doi. org/10.1111/j.1365-2567.2010.03357.x
58. Alderson KL, Luangrath M, Elsenheimer MM, Gillies SD, Navid F, Rakhmilevich AL, Sondel PM. Enhancement of the anti-melanoma response of Hu14.18K322A by aCD40 + CpG. Cancer Immunol Immunother 2013; 62:665-75; PMID:23151945; http://dx.doi.org/10.1007/s00262-012-1372-8
59. Beatty GL, Chiorean EG, Fishman MP, Saboury B, Teitelbaum UR, Sun W, Huhn RD, Song W, Li D, Sharp LL, et al. CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science 2011; 331:1612-6; PMID:21436454; http://dx.doi.org/10.1126/ science.1198443
60. Sharma MD, Hou DY, Baban B, Koni PA, He Y, Chandler PR, Blazar BR, Mellor AL, Munn DH. Reprogrammed foxp3(+) regulatory T cells provide essential help to support cross-presentation and CD8(+) T cell priming in naive mice. Immunity 2010; 33:942-54; PMID:21145762; http://dx.doi. org/10.1016/j.immuni.2010.11.022
61. Sharma MD, Hou DY, Liu Y, Koni PA, Metz R, Chandler P, Mellor AL, He Y, Munn DH. Indoleamine 2,3-dioxygenase controls conversion of Foxp3+ Tregs to TH17-like cells in tumor-draining lymph nodes. Blood 2009; 113:6102-11; PMID:19366986; http:// dx.doi.org/10.1182/blood-2008-12-195354
62. Ko HJ, Kim YJ, Kim YS, Chang WS, Ko SY, Chang SY, Sakaguchi S, Kang CY. A combination of chemoimmunotherapies can efficiently break self-tolerance and induce antitumor immunity in a tolerogenic murine tumor model. Cancer Res 2007; 67:7477-86; PMID:17671218; http://dx.doi. org/10.1158/0008-5472.CAN-06-4639
63. Huang H, Li F, Gordon JR, Xiang J. Synergistic enhancement of antitumor immunity with adoptively transferred tumor-specific CD4+ and CD8+ T cells and intratumoral lymphotactin transgene expression. Cancer Res 2002; 62:2043-51; PMID:11929823
64. Huang H, Xiang J. Synergistic effect of lymphotactin and interferon gamma-inducible protein-10 transgene expression in T-cell localization and adoptive T-cell therapy of tumors. Int J Cancer 2004; 109:817-25; PMID:15027114; http://dx.doi.org/10.1002/ ijc.20043
65. Narvaiza I, Mazzolini G, Barajas M, Duarte M, Zaratiegui M, Qian C, Melero I, Prieto J. Intratumoral coinjection of two adenoviruses, one encoding the chemokine IFN-gamma-inducible protein-10 and another encoding IL-12, results in marked antitumoral synergy. J Immunol 2000; 164:3112-22; PMID:10706701
66. Palmer K, Hitt M, Emtage PC, Gyorffy S, Gauldie J. Combined CXC chemokine and interleukin-12 gene transfer enhances antitumor immunity. Gene Ther 2001; 8:282-90; PMID:11313802; http://dx.doi. org/10.1038/sj.gt.3301386
67. Liu Y, Huang H, Saxena A, Xiang J. Intratumoral coinjection of two adenoviral vectors expressing functional interleukin-18 and inducible protein-10, respectively, synergizes to facilitate regression of established tumors. Cancer Gene Ther 2002; 9:533-42; PMID:12032664; http://dx.doi.org/10.1038/ sj.cgt.7700466
68. Jiang XB, Lu XL, Hu P, Liu RE. Improved therapeutic efficacy using vaccination with glioma lysate-pulsed dendritic cells combined with IP-10 in murine glioma. Vaccine 2009; 27:6210-6; PMID:19699331; http://dx.doi.org/10.1016/j.vaccine.2009.08.002
69. Li J, O'Malley M, Urban J, Sampath P, Guo ZS, Kalinski P, Thorne SH, Bartlett DL. Chemokine expression from oncolytic vaccinia virus enhances vaccine therapies of cancer. Mol Ther 2011; 19:650-7; PMID:21266959; http://dx.doi.org/10.1038/ mt.2010.312
70. Parker JN, Meleth S, Hughes KB, Gillespie GY, Whitley RJ, Markert JM. Enhanced inhibition of syngeneic murine tumors by combinatorial therapy with genetically engineered HSV-1 expressing CCL2 and IL-12. Cancer Gene Ther 2005; 12:359-68; PMID:15678154; http://dx.doi.org/10.1038/ sj.cgt.7700784
71. Oh SM, Oh K, Lee DS. Intratumoral administration of secondary lymphoid chemokine and unmethylated cytosine-phosphorothioate-guanine oligodeoxynucleotide synergistically inhibits tumor growth in vivo. J Korean Med Sci 2011; 26:1270-6; PMID:22022177; http://dx.doi.org/10.3346/ jkms.2011.26.10.1270
72. Rakoff-Nahoum S, Medzhitov R. Toll-like receptors and cancer. Nat Rev Cancer 2009; 9:57-63; PMID:19052556; http://dx.doi.org/10.1038/ nrc2541
73. Lou Y, Liu C, Lizée G, Peng W, Xu C, Ye Y, Rabinovich BA, Hailemichael Y, Gelbard A, Zhou D, et al. Antitumor activity mediated by CpG: the route of administration is critical. J Immunother 2011; 34:279-88; PMID:21389870; http://dx.doi. org/10.1097/CJI.0b013e31820d2a05
74. Amos SM, Pegram HJ, Westwood JA, John LB, Devaud C, Clarke CJ, Restifo NP, Smyth MJ, Darcy PK, Kershaw MH. Adoptive immunotherapy combined with intratumoral TLR agonist delivery eradicates established melanoma in mice. Cancer Immunol Immunother 2011; 60:671-83; PMID:21327636; http://dx.doi.org/10.1007/ s00262-011-0984-8
75. Stone GW, Barzee S, Snarsky V, Santucci C, Tran B, Langer R, Zugates GT, Anderson DG, Kornbluth RS. Nanoparticle-delivered multimeric soluble CD40L DNA combined with Toll-Like Receptor agonists as a treatment for melanoma. PLoS One 2009; 4:e7334; PMID:19812695; http://dx.doi.org/10.1371/journal. pone.0007334
76. Kirn DH, Thorne SH. Targeted and armed oncolytic poxviruses: a novel multi-mechanistic therapeutic class for cancer. Nat Rev Cancer 2009; 9:64-71; PMID:19104515; http://dx.doi.org/10.1038/nrc2545
77. John LB, Howland LJ, Flynn JK, West AC, Devaud C, Duong CP, Stewart TJ, Westwood JA, Guo ZS, Bartlett DL, et al. Oncolytic virus and anti-4-1BB combination therapy elicits strong antitumor immunity against established cancer. Cancer Res 2012; 72:1651-60; PMID:22315352; http://dx.doi. org/10.1158/0008-5472.CAN-11-2788
78. Thomas DL, Doty R, Tosic V, Liu J, Kranz DM, McFadden G, Macneill AL, Roy EJ. Myxoma virus combined with rapamycin treatment enhances adoptive T cell therapy for murine melanoma brain tumors. Cancer Immunol Immunother 2011; 60:1461-72; PMID:21656158; http://dx.doi. org/10.1007/s00262-011-1045-z
79. Qiao J, Wang H, Kottke T, Diaz RM, Willmon C, Hudacek A, Thompson J, Parato K, Bell J, Naik J, et al. Loading of oncolytic vesicular stomatitis virus onto antigen-specific T cells enhances the efficacy of adoptive T-cell therapy of tumors. Gene Ther 2008; 15:604-16; PMID:18305577; http://dx.doi. org/10.1038/sj.gt.3303098
80. Thorne SH, Negrin RS, Contag CH. Synergistic antitumor effects of immune cell-viral biotherapy. Science 2006; 311:1780-4; PMID:16556847; http:// dx.doi.org/10.1126/science.1121411
81. Cole C, Qiao J, Kottke T, Diaz RM, Ahmed A, Sanchez-Perez L, Brunn G, Thompson J, Chester J, Vile RG. Tumor-targeted, systemic delivery of therapeutic viral vectors using hitchhiking on antigen-specific T cells. Nat Med 2005; 11:1073-81; PMID:16170322; http://dx.doi.org/10.1038/ nm1297
82. Uno T, Takeda K, Kojima Y, Yoshizawa H, Akiba H, Mittler RS, Gejyo F, Okumura K, Yagita H, Smyth MJ. Eradication of established tumors in mice by a combination antibody-based therapy. Nat Med 2006; 12:693-8; PMID:16680149; http://dx.doi. org/10.1038/nm1405
83. Wilson NS, Yang A, Yang B, Couto S, Stern H, Gogineni A, Pitti R, Marsters S, Weimer RM, Singh M, et al. Proapoptotic activation of death receptor 5 on tumor endothelial cells disrupts the vasculature and reduces tumor growth. Cancer Cell 2012; 22:80-90; PMID:22789540; http://dx.doi.org/10.1016/j. ccr.2012.05.014
84. Chmielewski M, Kopecky C, Hombach AA, Abken H. IL-12 release by engineered T cells expressing chimeric antigen receptors can effectively Muster an antigen-independent macrophage response on tumor cells that have shut down tumor antigen expression. Cancer Res 2011; 71:5697-706; PMID:21742772; http://dx.doi.org/10.1158/0008-5472.CAN-11-0103
85. Kerkar SP, Goldszmid RS, Muranski P, Chinnasamy D, Yu Z, Reger RN, Leonardi AJ, Morgan RA, Wang E, Marincola FM, et al. IL-12 triggers a programmatic change in dysfunctional myeloid-derived cells within mouse tumors. J Clin Invest 2011; 121:4746-57; PMID:22056381; http://dx.doi.org/10.1172/ JCI58814
86. Dubrot J, Palazón A, Alfaro C, Azpilikueta A, Ochoa MC, Rouzaut A, Martinez-Forero I, Teijeira A, Berraondo P, Le Bon A, et al. Intratumoral injection of interferon-a and systemic delivery of agonist anti-CD137 monoclonal antibodies synergize for immunotherapy. Int J Cancer 2011; 128:105-18; PMID:20309938; http://dx.doi.org/10.1002/ ijc.25333
87. Kuwashima N, Nishimura F, Eguchi J, Sato H, Hatano M, Tsugawa T, Sakaida T, Dusak JE, Fellows-Mayle WK, Papworth GD, et al. Delivery of dendritic cells engineered to secrete IFN-alpha into central nervous system tumors enhances the efficacy of peripheral tumor cell vaccines: dependence on apoptotic pathways. J Immunol 2005; 175:2730-40; PMID:16081851
88. Flavell RA, Sanjabi S, Wrzesinski SH, Licona-Limón P. The polarization of immune cells in the tumour environment by TGFbeta. Nat Rev Immunol 2010; 10:554-67; PMID:20616810; http://dx.doi. org/10.1038/nri2808
89. Llopiz D, Dotor J, Casares N, Bezunartea J, Díaz-Valdés N, Ruiz M, Aranda F, Berraondo P, Prieto J, Lasarte JJ, et al. Peptide inhibitors of transforming growth factor-beta enhance the efficacy of antitumor immunotherapy. Int J Cancer 2009; 125:2614-23; PMID:19530254; http://dx.doi.org/10.1002/ ijc.24656
90. Park J, Wrzesinski SH, Stern E, Look M, Criscione J, Ragheb R, Jay SM, Demento SL, Agawu A, Licona Limon P, et al. Combination delivery of TGF-ß inhibitor and IL-2 by nanoscale liposomal polymeric gels enhances tumour immunotherapy. Nat Mater 2012; 11:895-905; PMID:22797827; http://dx.doi. org/10.1038/nmat3355
91. Berraondo P, Umansky V, Melero I. Changing the tumor microenvironment: new strategies for immunotherapy. Cancer Res 2012; 72:5159-64; PMID:22826606; http://dx.doi.org/10.1158/0008-5472.CAN-12-1952
92. Martinez Forero I, Okada H, Topalian SL, Gajewski TF, Korman AJ, Melero I. Workshop on immunotherapy combinations. Society for Immunotherapy of Cancer annual meeting Bethesda, November 3, 2011. J Transl Med 2012; 10:108; PMID:22640522; http://dx.doi. org/10.1186/1479-5876-10-108
93. Hodi FS, Friedlander PA, Atkins MB, McDermott DF, Lawrence DP, Ibrahim N, et al. A phase I trial of ipilimumab plus bevacizumab in patients with unresectable stage III or stage IV melanoma. [Suppl.]. J Clin Oncol 2011; 29:8511
94. Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM, Segal NH, Ariyan CE, Gordon RA, Reed K, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med 2013; 369:122-33; PMID:23724867; http://dx.doi. org/10.1056/NEJMoa1302369
95. Picozzi VJ, Kozarek RA, Traverso LW. Interferonbased adjuvant chemoradiation therapy after pancreaticoduodenectomy for pancreatic adenocarcinoma. Am J Surg 2003; 185:476-80; PMID:12727570; http://dx.doi.org/10.1016/ S0002-9610(03)00051-5
96. Chinnasamy D, Yu Z, Kerkar SP, Zhang L, Morgan RA, Restifo NP, Rosenberg SA. Local delivery of interleukin-12 using T cells targeting VEGF receptor-2 eradicates multiple vascularized tumors in mice. Clin Cancer Res 2012; 18:1672-83; PMID:22291136; http://dx.doi.org/10.1158/1078-0432.CCR-11-3050
97. Zhang L, Kerkar SP, Yu Z, Zheng Z, Yang S, Restifo NP, Rosenberg SA, Morgan RA. Improving adoptive T cell therapy by targeting and controlling IL-12 expression to the tumor environment. Mol Ther 2011; 19:751-9; PMID:21285960; http://dx.doi. org/10.1038/mt.2010.313