Modern radiotherapy concepts and the impact of radiation on immune activation

Frontiers in Oncology

Volumn 6, Issue JUN, 2016, Pages

  Deloch, Lisa ^a   Derer, Anja ^a   Hartmann, Josefin ^a   Frey, Benjamin ^a   Fietkau, Rainer ^a   Gaipl, Udo S ^a  

^a UNIVERSITY HOSPITAL ERLANGEN   (Germany)

Author keywords

Abscopal effect; Anti tumor immunity; Norm and hypofractionation; Radiotherapy; SABR

Indexed keywords

CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; GAMMA INTERFERON; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; INTERLEUKIN 12P70; INTERLEUKIN 1BETA; INTERLEUKIN 6; INTERLEUKIN 8; TOLL LIKE RECEPTOR; TUMOR NECROSIS FACTOR ALPHA;

ANTIGEN PRESENTING CELL; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; AUTOPHAGY; CANCER RADIOTHERAPY; COMPUTER ASSISTED RADIOTHERAPY; DNA DAMAGE; EFFECTIVE DOSE (RADIATION); HEAD AND NECK SQUAMOUS CELL CARCINOMA; HUMAN; IMAGE GUIDED RADIOTHERAPY; IMMUNE RESPONSE; IMMUNOSENESCENCE; INTENSITY MODULATED RADIATION THERAPY; NECROSIS; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); RADIATION DOSE FRACTIONATION; RADIOSENSITIVITY; RADIOSURGERY; REVIEW; STEREOTACTIC BODY RADIATION THERAPY; T LYMPHOCYTE ACTIVATION; TUMOR IMMUNITY; TUMOR MICROENVIRONMENT;

EID: 84982792265     PISSN: None     EISSN: 2234943X     Source Type: Journal    
DOI: 10.3389/fonc.2016.00141     Document Type: Review

References (120)

1. Eriksson D, Stigbrand T. Radiation-induced cell death mechanisms. Tumour Biol (2010) 31(4):363-72. doi:10.1007/s13277-010-0042-8
2. Balcer-Kubiczek EK. Apoptosis in radiation therapy: a double-edged sword. Exp Oncol (2012) 34(3):277-85.
3. Jonathan EC, Bernhard EJ, McKenna WG. How does radiation kill cells? Curr Opin Chem Biol (1999) 3(1):77-83. doi:10.1016/S1367-5931(99)80014-3
4. Prasanna A, Ahmed MM, Mohiuddin M, Coleman CN. Exploiting sensitization windows of opportunity in hyper and hypo-fractionated radiation therapy. J Thorac Dis (2014) 6(4):287-302. doi:10.3978/j.issn.2072-1439.2014.01.14
5. Orth M, Lauber K, Niyazi M, Friedl AA, Li M, Maihofer C, et al. Current concepts in clinical radiation oncology. Radiat Environ Biophys (2014) 53(1):1-29. doi:10.1007/s00411-013-0497-2
6. Derer A, Frey B, Fietkau R, Gaipl US. Immune-modulating properties of ionizing radiation: rationale for the treatment of cancer by combination radiotherapy and immune checkpoint inhibitors. Cancer Immunol Immunother (2015). doi:10.1007/s00262-015-1771-8
7. Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer (1972) 26(4):239-57. doi:10.1038/bjc.1972.33
8. Verheij M, Bartelink H. Radiation-induced apoptosis. Cell Tissue Res (2000) 301(1):133-42. doi:10.1007/s004410000188
9. Lauber K, Ernst A, Orth M, Herrmann M, Belka C. Dying cell clearance and its impact on the outcome of tumor radiotherapy. Front Oncol (2012) 2:116. doi:10.3389/fonc.2012.00116
10. Erwig LP, Henson PM. Clearance of apoptotic cells by phagocytes. Cell Death Differ (2008) 15(2):243-50. doi:10.1038/sj.cdd.4402184
11. Voll RE, Herrmann M, Roth EA, Stach C, Kalden JR, Girkontaite I. Immunosuppressive effects of apoptotic cells. Nature (1997) 390(6658):350-1. doi:10.1038/37022
12. Igney FH, Krammer PH. Death and anti-death: tumour resistance to apoptosis. Nat Rev Cancer (2002) 2(4):277-88. doi:10.1038/nrc776
13. Dewey WC, Ling CC, Meyn RE. Radiation-induced apoptosis: relevance to radiotherapy. Int J Radiat Oncol Biol Phys (1995) 33(4):781-96. doi:10.1016/0360-3016(95)00214-8
14. Kroemer G, Galluzzi L, Vandenabeele P, Abrams J, Alnemri ES, Baehrecke EH, et al. Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009. Cell Death Differ (2009) 16(1):3-11. doi:10.1038/cdd.2008.150
15. Krysko O, Love Aaes T, Bachert C, Vandenabeele P, Krysko DV. Many faces of DAMPs in cancer therapy. Cell Death Dis (2013) 4:e631. doi:10.1038/cddis.2013.156
16. Proskuryakov SY, Konoplyannikov AG, Gabai VL. Necrosis: a specific form of programmed cell death? Exp Cell Res (2003) 283(1):1-16. doi:10.1016/S0014-4827(02)00027-7
17. Ianzini F, Bertoldo A, Kosmacek EA, Phillips SL, Mackey MA. Lack of p53 function promotes radiation-induced mitotic catastrophe in mouse embryonic fibroblast cells. Cancer Cell Int (2006) 6:11. doi:10.1186/1475-2867-6-11
18. Mc Gee MM. Targeting the mitotic catastrophe signaling pathway in cancer. Mediators Inflamm (2015) 2015:146282. doi:10.1155/2015/146282
19. Gewirtz DA, Holt SE, Elmore LW. Accelerated senescence: an emerging role in tumor cell response to chemotherapy and radiation. Biochem Pharmacol (2008) 76(8):947-57. doi:10.1016/j.bcp.2008.06.024
20. Fulda S, Kogel D. Cell death by autophagy: emerging molecular mechanisms and implications for cancer therapy. Oncogene (2015) 34(40):5105-13. doi:10.1038/onc.2014.458
21. Huang YH, Yang PM, Chuah QY, Lee YJ, Hsieh YF, Peng CW, et al. Autophagy promotes radiation-induced senescence but inhibits bystander effects in human breast cancer cells. Autophagy (2014) 10(7):1212-28. doi:10.4161/auto.28772
22. Gewirtz DA. The four faces of autophagy: implications for cancer therapy. Cancer Res (2014) 74(3):647-51. doi:10.1158/0008-5472.can-13-2966
23. Roos WP, Thomas AD, Kaina B. DNA damage and the balance between survival and death in cancer biology. Nat Rev Cancer (2016) 16(1):20-33. doi:10.1038/nrc.2015.2
24. Figueiredo N, Chora A, Raquel H, Pejanovic N, Pereira P, Hartleben B, et al. Anthracyclines induce DNA damage response-mediated protection against severe sepsis. Immunity (2013) 39(5):874-84. doi:10.1016/j.immuni.2013.08.039
25. Gewirtz DA. The autophagic response to radiation: relevance for radiation sensitization in cancer therapy. Radiat Res (2014) 182(4):363-7. doi:10.1667/rr13774.1
26. Rodel F, Frey B, Multhoff G, Gaipl U. Contribution of the immune system to bystander and non-targeted effects of ionizing radiation. Cancer Lett (2015) 356(1):105-13. doi:10.1016/j.canlet.2013.09.015
27. Golden EB, Apetoh L. Radiotherapy and immunogenic cell death. Semin Radiat Oncol (2015) 25(1):11-7. doi:10.1016/j.semradonc.2014.07.005
28. Gaipl US, Multhoff G, Scheithauer H, Lauber K, Hehlgans S, Frey B, et al. Kill and spread the word: stimulation of antitumor immune responses in the context of radiotherapy. Immunotherapy (2014) 6(5):597-610. doi:10.2217/imt.14.38
29. del Regato JA. Albert Soiland and the early development of therapeutic radiology in the United States. Int J Radiat Oncol Biol Phys (1983) 9(2):243-53. doi:10.1016/0360-3016(83)90106-2
30. Thariat J, Hannoun-Levi JM, Sun Myint A, Vuong T, Gerard JP. Past, present, and future of radiotherapy for the benefit of patients. Nat Rev Clin Oncol (2013) 10(1):52-60. doi:10.1038/nrclinonc.2012.203
31. Bernier J, Hall EJ, Giaccia A. Radiation oncology: a century of achievements. Nat Rev Cancer (2004) 4(9):737-47. doi:10.1038/nrc1451
32. Bergonie J, Tribondeau L. Interpretation of some results from radiotherapy and an attempt to determine a rational treatment technique. 1906. Yale J Biol Med (2003) 76(4-6):181-2.
33. Rodger A. Fears over radiotherapy fractionation regimens in breast cancer: proposed UK trial needs to define techniques as well as numbers of treatments. BMJ (1998) 317(7152):155-6. doi:10.1136/bmj.317.7152.155
34. Coutard H. Principles of X ray therapy of malignant diseases. Lancet (1934) 224(5784):1-8. doi:10.1016/S0140-6736(00)90085-0
35. Baclesse F. Comparative study of results obtained with conventional radiotherapy (200 KV) and cobalt therapy in the treatment of cancer of the larynx. Clin Radiol (1967) 18(3):292-300. doi:10.1016/S0009-9260(67)80077-1
36. Barendsen GW. Dose fractionation, dose rate and iso-effect relationships for normal tissue responses. Int J Radiat Oncol Biol Phys (1982) 8(11):1981-97. doi:10.1016/0360-3016(82)90459-X
37. Brahme A. Optimization of stationary and moving beam radiation therapy techniques. Radiother Oncol (1988) 12(2):129-40. doi:10.1016/0167-8140(88)90167-3
38. Otto K. Volumetric modulated arc therapy: IMRT in a single gantry arc. Med Phys (2008) 35(1):310-7. doi:10.1118/1.2818738
39. Palma D, Vollans E, James K, Nakano S, Moiseenko V, Shaffer R, et al. Volumetric modulated arc therapy for delivery of prostate radiotherapy: comparison with intensity-modulated radiotherapy and three-dimensional conformal radiotherapy. Int J Radiat Oncol Biol Phys (2008) 72(4):996-1001. doi:10.1016/j.ijrobp.2008.02.047
40. Ikushima H. Radiation therapy: state of the art and the future. J Med Invest (2010) 57(1-2):1-11. doi:10.2152/jmi.57.1
41. Timmerman RD, Herman J, Cho LC. Emergence of stereotactic body radiation therapy and its impact on current and future clinical practice. J Clin Oncol (2014) 32(26):2847-54. doi:10.1200/jco.2014.55.4675
42. Muller-Runkel R, Vijayakumar S. Equivalent total doses for different fractionation schemes, based on the linear quadratic model. Radiology (1991) 179(2):573-7. doi:10.1148/radiology.179.2.2014314
43. Dorr W, Baumann M, Herrmann T. [Nomenclature of modified fractionation protocols in radiotherapy]. Strahlenther Onkol (1996) 172(7):353-5.
44. Brown JM, Carlson DJ, Brenner DJ. The tumor radiobiology of SRS and SBRT: are more than the 5 Rs involved? Int J Radiat Oncol Biol Phys (2014) 88(2):254-62. doi:10.1016/j.ijrobp.2013.07.022
45. Dovedi SJ, Adlard AL, Lipowska-Bhalla G, McKenna C, Jones S, Cheadle EJ, et al. Acquired resistance to fractionated radiotherapy can be overcome by concurrent PD-L1 blockade. Cancer Res (2014) 74(19):5458-68. doi:10.1158/0008-5472.can-14-1258
46. Douglas BG, Fowler JF. The effect of multiple small doses of x rays on skin reactions in the mouse and a basic interpretation. Radiat Res (1976) 66(2):401-26. doi:10.2307/3574407
47. Bentzen SM, Dorr W, Gahbauer R, Howell RW, Joiner MC, Jones B, et al. Bioeffect modeling and equieffective dose concepts in radiation oncology-terminology, quantities and units. Radiother Oncol (2012) 105(2):266-8. doi:10.1016/j.radonc.2012.10.006
48. Jones B, Dale RG, Deehan C, Hopkins KI, Morgan DA. The role of biologically effective dose (BED) in clinical oncology. Clin Oncol (R Coll Radiol) (2001) 13(2):71-81. doi:10.1053/clon.2001.9221
49. Vesely MD, Schreiber RD. Cancer immunoediting: antigens, mechanisms, and implications to cancer immunotherapy. Ann N Y Acad Sci (2013) 1284:1-5. doi:10.1111/nyas.12105
50. Trowell OA. The sensitivity of lymphocytes to ionising radiation. J Pathol Bacteriol (1952) 64(4):687-704. doi:10.1002/path.1700640403
51. Mendes F, Antunes C, Abrantes AM, Goncalves AC, Nobre-Gois I, Sarmento AB, et al. Lung cancer: the immune system and radiation. Br J Biomed Sci (2015) 72(2):78-84. doi:10.1080/09674845.2015.11666801
52. Derer A, Deloch L, Rubner Y, Fietkau R, Frey B, Gaipl US. Radio-immunotherapy-induced immunogenic cancer cells as basis for induction of systemic anti-tumor immune responses-pre-clinical evidence and ongoing clinical applications. Front Immunol (2015) 6:505. doi:10.3389/fimmu.2015.00505
53. Multhoff G, Gaipl US, Niedermann G. [The role of radiotherapy in the induction of antitumor immune responses]. Strahlenther Onkol (2012) 188(Suppl 3):312-5. doi:10.1007/s00066-012-0206-0
54. Vatner RE, Cooper BT, Vanpouille-Box C, Demaria S, Formenti SC. Combinations of immunotherapy and radiation in cancer therapy. Front Oncol (2014) 4:325. doi:10.3389/fonc.2014.00325
55. Kaminski JM, Shinohara E, Summers JB, Niermann KJ, Morimoto A, Brousal J. The controversial abscopal effect. Cancer Treat Rev (2005) 31(3):159-72. doi:10.1016/j.ctrv.2005.03.004
56. Demaria S, Ng B, Devitt ML, Babb JS, Kawashima N, Liebes L, et al. Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated. Int J Radiat Oncol Biol Phys (2004) 58(3):862-70. doi:10.1016/j.ijrobp.2003.09.012
57. Frey B, Gaipl US. Radio-immunotherapy: the focused beam expands. Lancet Oncol (2015) 16(7):742-3. doi:10.1016/s1470-2045(15)00055-8
58. Formenti SC, Demaria S. Systemic effects of local radiotherapy. Lancet Oncol (2009) 10(7):718-26. doi:10.1016/s1470-2045(09)70082-8
59. Manda K, Glasow A, Paape D, Hildebrandt G. Effects of ionizing radiation on the immune system with special emphasis on the interaction of dendritic and T cells. Front Oncol (2012) 2:102. doi:10.3389/fonc.2012.00102
60. Cao MD, Chen ZD, Xing Y. Gamma irradiation of human dendritic cells influences proliferation and cytokine profile of T cells in autologous mixed lymphocyte reaction. Cell Biol Int (2004) 28(3):223-8. doi:10.1016/j.cellbi.2003.12.006
61. Lugade AA, Moran JP, Gerber SA, Rose RC, Frelinger JG, Lord EM. Local radiation therapy of B16 melanoma tumors increases the generation of tumor antigen-specific effector cells that traffic to the tumor. J Immunol (2005) 174(12):7516-23. doi:10.4049/jimmunol.174.12.7516
62. Liao YP, Wang CC, Schaue D, Iwamoto KS, McBride WH. Local irradiation of murine melanoma affects the development of tumour-specific immunity. Immunology (2009) 128(1 Suppl):e797-804. doi:10.1111/j.1365-2567.2009.03084.x
63. Lee Y, Auh SL, Wang Y, Burnette B, Wang Y, Meng Y, et al. Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment. Blood (2009) 114(3):589-95. doi:10.1182/blood-2009-02-206870
64. Falcke S, Rühle PF, Frey B, Fietkau R, Gaipl US. Human peripheral blood immune cells strongly differ in their radiosensitivity. Strahlenther Onkol (2015) 191(Suppl 1):1-184. doi:10.1007/s00066-015-0847-x
65. Bauer M, Goldstein M, Christmann M, Becker H, Heylmann D, Kaina B. Human monocytes are severely impaired in base and DNA double-strand break repair that renders them vulnerable to oxidative stress. Proc Natl Acad Sci U S A (2011) 108(52):21105-10. doi:10.1073/pnas.1111919109
66. Wunderlich R, Ernst A, Rodel F, Fietkau R, Ott O, Lauber K, et al. Low and moderate doses of ionizing radiation up to 2 Gy modulate transmigration and chemotaxis of activated macrophages, provoke an anti-inflammatory cytokine milieu, but do not impact upon viability and phagocytic function. Clin Exp Immunol (2015) 179(1):50-61. doi:10.1111/cei.12344
67. Merrick A, Errington F, Milward K, O'Donnell D, Harrington K, Bateman A, et al. Immunosuppressive effects of radiation on human dendritic cells: reduced IL-12 production on activation and impairment of naive T-cell priming. Br J Cancer (2005) 92(8):1450-8. doi:10.1038/sj.bjc.6602518
68. Deng L, Liang H, Burnette B, Beckett M, Darga T, Weichselbaum RR, et al. Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. J Clin Invest (2014) 124(2):687-95. doi:10.1172/jci67313
69. Vatner RE, Formenti SC. Myeloid-derived cells in tumors: effects of radiation. Semin Radiat Oncol (2015) 25(1):18-27. doi:10.1016/j.semradonc.2014.07.008
70. Hedberg ML, Goh G, Chiosea SI, Bauman JE, Freilino ML, Zeng Y, et al. Genetic landscape of metastatic and recurrent head and neck squamous cell carcinoma. J Clin Invest (2016) 126(1):169-80. doi:10.1172/jci82066
71. Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, et al. Signatures of mutational processes in human cancer. Nature (2013) 500(7463):415-21. doi:10.1038/nature12477
72. Al-Ejeh F, Shi W, Miranda M, Simpson PT, Vargas AC, Song S, et al. Treatment of triple-negative breast cancer using anti-EGFR-directed radioimmunotherapy combined with radiosensitizing chemotherapy and PARP inhibitor. J Nucl Med (2013) 54(6):913-21. doi:10.2967/jnumed.112.111534
73. Bloy N, Pol J, Manic G, Vitale I, Eggermont A, Galon J, et al. Trial watch: radioimmunotherapy for oncological indications. Oncoimmunology (2014) 3(9):e954929. doi:10.4161/21624011.2014.954929
74. Norihisa Y, Nagata Y, Takayama K, Matsuo Y, Sakamoto T, Sakamoto M, et al. Stereotactic body radiotherapy for oligometastatic lung tumors. Int J Radiat Oncol Biol Phys (2008) 72(2):398-403. doi:10.1016/j.ijrobp.2008.01.002
75. Hodge JW, Garnett CT, Farsaci B, Palena C, Tsang KY, Ferrone S, et al. Chemotherapy-induced immunogenic modulation of tumor cells enhances killing by cytotoxic T lymphocytes and is distinct from immunogenic cell death. Int J Cancer (2013) 133(3):624-36. doi:10.1002/ijc.28070
76. Gameiro SR, Ardiani A, Kwilas A, Hodge JW. Radiation-induced survival responses promote immunogenic modulation to enhance immunotherapy in combinatorial regimens. Oncoimmunology (2014) 3:e28643. doi:10.4161/onci.28643
77. Hellevik T, Martinez-Zubiaurre I. Radiotherapy and the tumor stroma: the importance of dose and fractionation. Front Oncol (2014) 4:1. doi:10.3389/fonc.2014.00001
78. Park HJ, Griffin RJ, Hui S, Levitt SH, Song CW. Radiation-induced vascular damage in tumors: implications of vascular damage in ablative hypofractionated radiotherapy (SBRT and SRS). Radiat Res (2012) 177(3):311-27. doi:10.1667/RR2773.1
79. Rubner Y, Muth C, Strnad A, Derer A, Sieber R, Buslei R, et al. Fractionated radiotherapy is the main stimulus for the induction of cell death and of Hsp70 release of p53 mutated glioblastoma cell lines. Radiat Oncol (2014) 9(1):89. doi:10.1186/1748-717x-9-89
80. Kulzer L, Rubner Y, Deloch L, Allgauer A, Frey B, Fietkau R, et al. Norm-and hypo-fractionated radiotherapy is capable of activating human dendritic cells. J Immunotoxicol (2014) 11(4):328-36. doi:10.3109/1547691x.2014.880533
81. Tsai MH, Cook JA, Chandramouli GV, DeGraff W, Yan H, Zhao S, et al. Gene expression profiling of breast, prostate, and glioma cells following single versus fractionated doses of radiation. Cancer Res (2007) 67(8):3845-52. doi:10.1158/0008-5472.can-06-4250
82. Deng L, Liang H, Xu M, Yang X, Burnette B, Arina A, et al. STING-dependent cytosolic DNA sensing promotes radiation-induced type I interferon-dependent antitumor immunity in immunogenic tumors. Immunity (2014) 41(5):843-52. doi:10.1016/j.immuni.2014.10.019
83. Haikerwal SJ, Hagekyriakou J, MacManus M, Martin OA, Haynes NM. Building immunity to cancer with radiation therapy. Cancer Lett (2015) 368(2):198-208. doi:10.1016/j.canlet.2015.01.009
84. Dewan MZ, Galloway AE, Kawashima N, Dewyngaert JK, Babb JS, Formenti SC, et al. Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody. Clin Cancer Res (2009) 15(17):5379-88. doi:10.1158/1078-0432.ccr-09-0265
85. Schaue D, Ratikan JA, Iwamoto KS, McBride WH. Maximizing tumor immunity with fractionated radiation. Int J Radiat Oncol Biol Phys (2012) 83(4):1306-10. doi:10.1016/j.ijrobp.2011.09.049
86. Frey B, Rubner Y, Wunderlich R, Weiss EM, Pockley AG, Fietkau R, et al. Induction of abscopal anti-tumor immunity and immunogenic tumor cell death by ionizing irradiation-implications for cancer therapies. Curr Med Chem (2012) 19(12):1751-64. doi:10.2174/092986712800099811
87. Shi W, Siemann DW. Augmented antitumor effects of radiation therapy by 4-1BB antibody (BMS-469492) treatment. Anticancer Res (2006) 26(5a):3445-53.
88. Witham TF, Okada H, Fellows W, Hamilton RL, Flickinger JC, Chambers WH, et al. The characterization of tumor apoptosis after experimental radiosurgery. Stereotact Funct Neurosurg (2005) 83(1):17-24. doi:10.1159/000084475
89. Park SS, Dong H, Liu X, Harrington SM, Krco CJ, Grams MP, et al. PD-1 restrains radiotherapy-induced abscopal effect. Cancer Immunol Res (2015) 3(6):610-9. doi:10.1158/2326-6066.cir-14-0138
90. Kotter B, Frey B, Winderl M, Rubner Y, Scheithauer H, Sieber R, et al. The in vitro immunogenic potential of caspase-3 proficient breast cancer cells with basal low immunogenicity is increased by hypofractionated irradiation. Radiat Oncol (2015) 10:197. doi:10.1186/s13014-015-0506-5
91. Aryankalayil MJ, Makinde AY, Gameiro SR, Hodge JW, Rivera-Solis PP, Palayoor ST, et al. Defining molecular signature of pro-immunogenic radiotherapy targets in human prostate cancer cells. Radiat Res (2014) 182(2):139-48. doi:10.1667/rr13731.1
92. Golden EB, Frances D, Pellicciotta I, Demaria S, Helen Barcellos-Hoff M, Formenti SC. Radiation fosters dose-dependent and chemotherapy-induced immunogenic cell death. Oncoimmunology (2014) 3:e28518. doi:10.4161/onci.28518
93. Reits EA, Hodge JW, Herberts CA, Groothuis TA, Chakraborty M, Wansley EK, et al. Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy. J Exp Med (2006) 203(5):1259-71. doi:10.1084/jem.20052494
94. Kumari A, Cacan E, Greer SF, Garnett-Benson C. Turning T cells on: epigenetically enhanced expression of effector T-cell costimulatory molecules on irradiated human tumor cells. J Immunother Cancer (2013) 1:17. doi:10.1186/2051-1426-1-17
95. Dewan MZ, Vanpouille-Box C, Kawashima N, DiNapoli S, Babb JS, Formenti SC, et al. 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(24):6668-78. doi:10.1158/1078-0432.ccr-12-0984
96. Filatenkov A, Baker J, Mueller AM, Kenkel J, Ahn GO, Dutt S, et al. Ablative tumor radiation can change the tumor immune cell microenvironment to induce durable complete remissions. Clin Cancer Res (2015) 21(16):3727-39. doi:10.1158/1078-0432.ccr-14-2824
97. Nikitina EY, Gabrilovich DI. Combination of gamma-irradiation and dendritic cell administration induces a potent antitumor response in tumor-bearing mice: approach to treatment of advanced stage cancer. Int J Cancer (2001) 94(6):825-33. doi:10.1002/1097-0215(20011215)94:6<825::AID-IJC1545>3.0.CO;2-5
98. Teitz-Tennenbaum S, Li Q, Rynkiewicz S, Ito F, Davis MA, McGinn CJ, et al. Radiotherapy potentiates the therapeutic efficacy of intratumoral dendritic cell administration. Cancer Res (2003) 63(23):8466-75.
99. Camphausen K, Moses MA, Menard C, Sproull M, Beecken WD, Folkman J, et al. Radiation abscopal antitumor effect is mediated through p53. Cancer Res (2003) 63(8):1990-3.
100. Peters LJ, Ang KK, Thames HD Jr. Accelerated fractionation in the radiation treatment of head and neck cancer. A critical comparison of different strategies. Acta Oncol (1988) 27(2):185-94. doi:10.3109/02841868809090339
101. Guckenberger M, Andratschke N, Alheit H, Holy R, Moustakis C, Nestle U, et al. Definition of stereotactic body radiotherapy: principles and practice for the treatment of stage I non-small cell lung cancer. Strahlenther Onkol (2014) 190(1):26-33. doi:10.1007/s00066-013-0450-y
102. Sterzing F, Brunner TB, Ernst I, Baus WW, Greve B, Herfarth K, et al. Stereotactic body radiotherapy for liver tumors: principles and practical guidelines of the DEGRO Working Group on Stereotactic Radiotherapy. Strahlenther Onkol (2014) 190(10):872-81. doi:10.1007/s00066-014-0714-1
103. Nobler MP. The abscopal effect in malignant lymphoma and its relationship to lymphocyte circulation. Radiology (1969) 93(2):410-2. doi:10.1148/93.2.410
104. Rubner Y, Wunderlich R, Ruhle PF, Kulzer L, Werthmoller N, Frey B, et al. How does ionizing irradiation contribute to the induction of anti-tumor immunity? Front Oncol (2012) 2:75. doi:10.3389/fonc.2012.00075
105. Konoeda K. [Therapeutic efficacy of pre-operative radiotherapy on breast carcinoma: in special reference to its abscopal effect on metastatic lymph-nodes]. Nihon Gan Chiryo Gakkai Shi (1990) 25(6):1204-14.
106. Okuma K, Yamashita H, Niibe Y, Hayakawa K, Nakagawa K. Abscopal effect of radiation on lung metastases of hepatocellular carcinoma: a case report. J Med Case Rep (2011) 5:111. doi:10.1186/1752-1947-5-111
107. Golden EB, Chhabra A, Chachoua A, Adams S, Donach M, Fenton-Kerimian M, 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(7):795-803. doi:10.1016/s1470-2045(15)00054-6
108. Grimaldi AM, Simeone E, Giannarelli D, Muto P, Falivene S, Borzillo V, et al. Abscopal effects of radiotherapy on advanced melanoma patients who progressed after ipilimumab immunotherapy. Oncoimmunology (2014) 3:e28780. doi:10.4161/onci.28780
109. Fu KK, Pajak TF, Marcial VA, Ortiz HG, Rotman M, Asbell SO, et al. Late effects of hyperfractionated radiotherapy for advanced head and neck cancer: long-term follow-up results of RTOG 83-13. Int J Radiat Oncol Biol Phys (1995) 32(3):577-88. doi:10.1016/0360-3016(95)00080-i
110. Beitler JJ, Zhang Q, Fu KK, Trotti A, Spencer SA, Jones CU, et al. Final results of local-regional control and late toxicity of RTOG 9003: a randomized trial of altered fractionation radiation for locally advanced head and neck cancer. Int J Radiat Oncol Biol Phys (2014) 89(1):13-20. doi:10.1016/j.ijrobp.2013.12.027
111. Fu KK, Pajak TF, Trotti A, Jones CU, Spencer SA, Phillips TL, et al. A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas: first report of RTOG 9003. Int J Radiat Oncol Biol Phys (2000) 48(1):7-16. doi:10.1016/S0360-3016(00)00663-5
112. Bourhis J, Overgaard J, Audry H, Ang KK, Saunders M, Bernier J, et al. Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis. Lancet (2006) 368(9538):843-54. doi:10.1016/s0140-6736(06)69121-6
113. Guckenberger M, Allgauer M, Appold S, Dieckmann K, Ernst I, Ganswindt U, et al. Safety and efficacy of stereotactic body radiotherapy for stage 1 non-small-cell lung cancer in routine clinical practice: a patterns-of-care and outcome analysis. J Thorac Oncol (2013) 8(8):1050-8. doi:10.1097/JTO.0b013e318293dc45
114. Haviland JS, Owen JR, Dewar JA, Agrawal RK, Barrett J, Barrett-Lee PJ, et al. The UK Standardisation of Breast Radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up results of two randomised controlled trials. Lancet Oncol (2013) 14(11):1086-94. doi:10.1016/s1470-2045(13)70386-3
115. Trovo M, Giaj-Levra N, Furlan C, Bortolin MT, Muraro E, Polesel J, et al. Stereotactic body radiation therapy and intensity modulated radiation therapy induce different plasmatic cytokine changes in non-small cell lung cancer patients: a pilot study. Clin Transl Oncol (2015). doi:10.1007/s12094-015-1473-x
116. Rule W, Timmerman R, Tong L, Abdulrahman R, Meyer J, Boike T, et al. Phase I dose-escalation study of stereotactic body radiotherapy in patients with hepatic metastases. Ann Surg Oncol (2011) 18(4):1081-7. doi:10.1245/s10434-010-1405-5
117. Chang DT, Swaminath A, Kozak M, Weintraub J, Koong AC, Kim J, et al. Stereotactic body radiotherapy for colorectal liver metastases: a pooled analysis. Cancer (2011) 117(17):4060-9. doi:10.1002/cncr.25997
118. Troost EG. [Stereotactic radiotherapy augments the immune response]. Strahlenther Onkol (2016) 192(1):70-1. doi:10.1007/s00066-015-0923-2
119. Sharabi AB, Nirschl CJ, Kochel CM, Nirschl TR, Francica BJ, Velarde E, et al. Stereotactic radiation therapy augments antigen-specific PD-1-mediated antitumor immune responses via cross-presentation of tumor antigen. Cancer Immunol Res (2015) 3(4):345-55. doi:10.1158/2326-6066.cir-14-0196
120. Barnett GC, West CM, Dunning AM, Elliott RM, Coles CE, Pharoah PD, et al. Normal tissue reactions to radiotherapy: towards tailoring treatment dose by genotype. Nat Rev Cancer (2009) 9(2):134-42. doi:10.1038/nrc2587