Radiation for awakening the dormant immune system, a promising challenge to be explored

Frontiers in Immunology

Volumn 5, Issue MAR, 2014, Pages

  de la Cruz Merino, Luis ^a   Illescas Vacas, Ana ^a   Grueso López, Ana ^a   Barco Sánchez, Antonio ^a   Míguez Sánchez, Carlos ^a  

^a HOSPITAL UNIVERSITARIO VIRGEN MACARENA   (Spain)

Author keywords

Abscopal effect; CTLA 4; Immunotherapy; Radiotherapy effects; Tumor microenvironment

Indexed keywords

ANTINEOPLASTIC AGENT; CALRETICULIN; CD134 ANTIGEN; CD137 ANTIBODY; CD137 ANTIGEN; CXCL16 CHEMOKINE; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; GAMMA INTERFERON; GLUCOCORTICOID INDUCED TUMOR NECROSIS FACTOR RECEPTOR; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; HIGH MOBILITY GROUP B1 PROTEIN; INTERLEUKIN 13; INTERLEUKIN 2; INTERLEUKIN 4; INTERLEUKIN 5; IPILIMUMAB; MELANOMA ANTIGEN 3; NATURAL KILLER CELL RECEPTOR NKG2D; NY ESO 1 ANTIGEN; OX40 ANTIBODY; PROGRAMMED DEATH 1 LIGAND 1; PROGRAMMED DEATH 1 LIGAND 1 ANTIBODY; T LYMPHOCYTE RECEPTOR; TOLL LIKE RECEPTOR 9; TOLL LIKE RECEPTOR AGONIST; UNCLASSIFIED DRUG;

CANCER RADIOTHERAPY; HUMAN; IMMUNE RESPONSE; IMMUNE SYSTEM; IMMUNOMODULATION; NONHUMAN; PHASE 3 CLINICAL TRIAL (TOPIC); RADIOIMMUNOTHERAPY; REVIEW; TUMOR IMMUNITY; TUMOR MICROENVIRONMENT;

EID: 84897950764     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2014.00102     Document Type: Review

References (75)

1. Formenti SC, Demaria S. Systemic effects of local RT. Lancet Oncol (2009) 10:718-26. doi:10.1016/S1470-2045(09)70082-8
2. Stone HB, Peters LJ, Milas L. Effect of host immune capability on radiocurability and subsequent transplantability of a murine fibrosarcoma. J Natl Cancer Inst (1979) 63:1229-35.
3. Steel GG, McMillan TJ, Peacock JH. The 5Rs of radiobiology. Int J Radiat Biol (1989) 56:1045-8. doi:10.1080/09553008914552491
4. Demaria S, Formenti SC. Radiation as an immunological adjuvant: current evidence on dose and fractionation. Front Oncol (2012) 2:153. doi:10.3389/fonc.2012.00153
5. Demaria S, Formenti SC. Sensors of ionizing radiation effects on the immunological microenvironment of cancer. Int J Radiat Biol (2007) 83:819-25. doi:10.1080/09553000701481816
6. Shiao SL, Coussens LM. The tumor-immune microenvironment and response to radiation therapy. J Mammary Gland Biol Neoplasia (2010) 15:411-21. doi:10.1007/s10911-010-9194-9
7. Demaria S, Bhardwaj N, McBride WH, Formenti SC. Combining RT and immunotherapy: a revived partnership. Int J Radiat Biol (2005) 63:655-6. doi:10.1016/j.ijrobp.2005.06.032
8. Matzinger P. Tolerance, danger, and the extended family. Annu Rev Immunol (1994) 12:991-1045. doi:10.1146/annurev.immunol.12.1.991
9. Tesniere A, Apetoh L, Ghiringhelli F, Joza N, Panaretakis T, Kepp O, et al. Immunogenic cancer cell death: a key-lock paradigm. Curr Opin Immunol (2008) 20:504-11. doi:10.1016/j.coi.2008.05.007
10. Obeid M. Ecto-calreticulin in immunogenic chemotherapy. Immunol Rev (2007) 220:22-34. doi:10.1111/j.1600-065X.2007.00567.x
11. Apetoh L, Ghiringhelli F, Tesniere A, Obeid M, Ortiz C, Criollo A, et al. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and RT. Nat Med (2007) 13:1050-9. doi:10.1038/nm1622
12. Gasser S, Orsulic S, Brown EJ, Raulet DH. The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor. Nature (2005) 436:1186-90. doi:10.1038/nature03884
13. Kim JY, Son YO, Park SW, Bae JH, Chung JS, Kim HH, et al. Increase of NKG2D ligands and sensitivity to NK cell-mediated cytotoxicity of tumor cells by heat shock and ionizing radiation. Exp Mol Med (2006) 38:474-474. doi:10.1038/emm.2006.56
14. Kessler B, Hudrisier D, Schroeter M, Tschopp J, Cerottini JC, Luescher IF. Peptide modification or blocking of CD8, resulting in weak TCR signaling, can activate CTL for Fas-but not perforin-dependent cytotoxicity or cytokine production. J Immunol (1998) 161:6939-46.
15. Larsson M, Fonteneau JF, Bhardwaj N. Dendritic cells resurrect antigens from dead cells. Trends Immunol (2001) 22:141-8. doi:10.1016/S1471-4906(01)01860-9
16. Skoberne M, Beignon AS, Bhardwaj N. Danger signals: a time and space continuum. Trends Mol Med (2004) 10:251-7. doi:10.1016/j.molmed.2004.04.001
17. Coates PJ, Rundle JK, Lorimore SA, Wright EG. Indirect macrophage responses to ionizing radiation: implications for genotype-dependent bystander signaling. Cancer Res (2008) 68:450-6. doi:10.1158/0008-5472.CAN-07-3050
18. Wright EG, Coates PJ. Untargeted effects of ionizing radiation: implications for radiation pathology. Mutat Res (2006) 597:119-32. doi:10.1016/j.mrfmmm.2005.03.035
19. Schaue D, Ratikan JA, Iwamoto KS, McBride WH. Maximizing tumor immunity with fractionated radiation. Int J Radiat Oncol Biol Phys (2012) 83:1306-10. doi:10.1016/j.ijrobp.2011.09.049
20. 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) 114:589-95. doi:10.1182/blood-2009-02-206870
21. Jobling MF, Mott JD, Finnegan MT, Jurukovski V, Erickson AC, Walian PJ, et al. Isoform-specific activation of latent transforming growth factor beta (LTGF-beta) by reactive oxygen species. Radiat Res (2006) 166:839-48. doi:10.1667/RR0695.1
22. Crittenden MR, Cottam B, Savage T, Nguyen C, Newell P, Gough MJ. Expression of NF-ΚB p50 in tumor stroma limits the control of tumors by radiation therapy. PLoS One (2012) 7:e39295. doi:10.1371/journal.pone.0039295
23. 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) 174:7516-23.
24. Matsumura S, Demaria S. Up-regulation of the pro-inflammatory chemokine CXCL16 is a common response of tumor cells to ionizing radiation. Radiat Res (2010) 173:418-25. doi:10.1667/RR1860.1
25. Matsumura S, Wang B, Kawashima N, Braunstein S, Badura M, Cameron TO, et al. Radiation-induced CXCL16 release by breast cancer cells attracts effector T cells. J Immunol (2008) 181:3099-107.
26. Demaria S, Kawashima N, Yang AM, Devitt ML, Babb JS, Allison JP, et al. Immune-mediated inhibition of metastases following treatment with local radiation and CTLA-4 blockade in a mouse model of breast cancer. Clin Cancer Res (2005) 11:728-34.
27. Chen Q, Wang WC, Evans SS. Tumor microvasculature as abarrier to antitumor immunity. Cancer Immunol Immunother (2003) 52:670-9. doi:10.1007/s00262-003-0425-4
28. Lugade AA, Sorensen EW, Gerber SA, Moran JP, Frelinger JG, Lord EM. Radiation-induced IFN-gamma production with in the tumor microenvironment influences anti-tumor immunity. J Immunol (2008) 180:3132-9.
29. Ahn GO, Tseng D, Liao CH, Dorie MJ, Czechowicz A, Brown JM. Inhibition of Mac-1 (CD11b/CD18) enhances tumor response to radiation by reducing myeloid cell recruitment. Proc Natl Acad Sci U S A (2010) 107:8363-8. doi:10.1073/pnas.0911378107
30. Chakraborty M, Abrams SI, Coleman CN, Camphausen K, Schlom J, Hodge JW. External beam radiation of tumors alters phenotype of tumor cells to render them susceptible to vaccine-mediated T-cell killing. Cancer Res (2004) 64:4328-37. doi:10.1158/0008-5472.CAN-04-0073
31. Sheard MA. Ionizing radiation as a response-enhancing agent for CD95-mediated apoptosis. Int J Cancer (2001) 96:213-20. doi:10.1002/ijc.1020
32. Friedman EJ. Immune modulation by ionizing radiation and its implications for cancer immunotherapy. Curr Pharm Des (2002) 8:1765-80. doi:10.2174/1381612023394089
33. Klug F, Prakash H, Huber PE, Seibel T, Bender N, Halama N, 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. doi:10.1016/j.ccr.2013.09.014
34. Belka C, Ottinger H, Kreuzfelder E, Weinmann M, Lindemann M, Lepple-Wienhues A, et al. Impact of localized RT on blood immune cells counts and function in humans. Radiother Oncol (1999) 50:199-204. doi:10.1016/S0167-8140(98)00130-3
35. DeNardo DG, Brennan DJ, Rexhepaj E, Ruffell B, Shiao SL, Madden SF, et al. Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy. Cancer Discovery (2011) 1:54-67. doi:10.1158/2159-8274.CD-10-0028
36. Hellstrom KE, Hellstrom I, Kant JA, Tamerius JD. Regression and inhibition of sarcoma growth by interference with a radiosensitive T-cell population. J Exp Med (1978) 148:799-804. doi:10.1084/jem.148.3.799
37. North RJ. Radiation-induced, immunologically mediated regression of an established tumor as an example of successful therapeutic immunomanipulation. Preferential elimination of suppressor T cells allows sustained production of effector T cells. J Exp Med (1986) 164:1652-66. doi:10.1084/jem.164.5.1652
38. Schaue D, Xie MW, Ratikan JA, McBride WH. Regulatory T cells in radiotherapeutic responses. Front Oncol (2012) 2:90. doi:10.3389/fonc.2012.00090
39. Schuler PJ, Harasymczuk M, Schilling B, Saze Z, Strauss L, Lang S, et al. Effects of adjuvant chemoRT on the frequency and function of regulatory T cells in patients with head and neck cancer. Clin Cancer Res (2013) 19:6585-96. doi:10.1158/1078-0432.CCR-13-0900
40. Chiang CS, Fu SY, Wang SC, Yu CF, Chen FH, Lin CM, et al. Irradiation promotes an M2 macrophage phenotype in tumor hypoxia. Front Oncol (2012) 6(2):89. doi:10.3389/fonc.2012.00089
41. Tsai CS, Chen FH, Wang CC, Huang HL, Jung SM, Wu CJ, et al. Macrophages from irradiated tumors express higher levels of iNOS, arginase-I and COX-2, and promote tumor growth. Int J Radiat Oncol Biol Phys (2007) 68:499-507. doi:10.1016/j.ijrobp.2007.01.041
42. Mole RJ. Whole body irradiation-radiology or medicine? Br J Radiol (1953) 26:234-41. doi:10.1259/0007-1285-26-305-234
43. Trosko JE, Chang CC, Upham BL, Tai MH. Low-dose ionizing radiation: Induction of differential intracellular signaling possibly affecting intercellular communication. Radiat Environ Biophys (2005) 44:3-9. doi:10.1007/s00411-005-0269-8
44. Kaminski JM, Shinohara E, Summers JB, Niermann KJ, Morimoto A, Brousal J. The controversial abscopal effect. Cancer Treat Rev (2005) 31:159-72. doi:10.1016/j.ctrv.2005.03.004
45. Lorimore SA, Chrystal JA, Robinson JI, Coates PJ, Wright EG. Chromosomal instability in unirradiated hemaopoietic cells induced by macrophages exposed in vivo to ionizing radiation. Cancer Res (2008) 68:8122-6. doi:10.1158/0008-5472.CAN-08-0698
46. Kingsley DP. An interesting case of possible abscopal effect in malignant melanoma. Br J Radiol (1975) 48:863-6. doi:10.1259/0007-1285-48-574-863
47. Robin HI, AuBuchon J, Varanasi VR, Weinstein AB. The abscopal effect: demonstration in lymphomatous involvement of kidneys. Med Pediatr Oncol (1981) 9:473-6. doi:10.1002/mpo.2950090510
48. Formenti SC, Demaria S. Radiation therapy to convert the tumor into an in situ vaccine. Int J Radiat Biol (2012) 84:879-80. doi:10.1016/j.ijrobp.2012.06.020
49. Camphausen K, Moses MA, Ménard C, Sproull M, Beecken WD, Folkman J, et al. Radiation abscopal antitumor effect is mediated through p53. Cancer Res (2003) 63:1990-3.
50. Ohba K, Omagari K, Nakamura T, Ikuno N, Saeki S, Matsuo I, et al. Abscopal regression of hepatocellular carcinoma after RT for bone metastasis. Gut (1998) 43:575-7. doi:10.1136/gut.43.4.575
51. Moret-Tatay I, Díaz J, Marco FM, Crespo A, Aliño SF. Complete tumor prevention by engineered tumor cell vaccines employing nonviral vectors. Cancer Gene Ther (2003) 10:887-97. doi:10.1038/sj.cgt.7700646
52. Tatsumi T, Huang J, Gooding WE, Gambotto A, Robbins PD, Vujanovic NL, et al. Intratumoral delivery of dendritic cells engineered to secrete both interleukin (IL)-12 and IL-18 effectively treats local and distant disease in association with broadly reactive Tc1-type immunity. Cancer Res (2003) 63:6378-86.
53. Hillman GG, Slos P, Wang Y, Wright JL, Layer A, De Meyer M, et al. Tumor irradiation followed by intratumoral cytokine gene therapy for murine renal adenocarcinoma. Cancer Gene Ther (2004) 11:61-72. doi:10.1038/sj.cgt.7700656
54. Nakanishi M, Chuma M, Hige S, Asaka M. Abscopal effect on hepatocellular carcinoma. Am J Gastroenterol (2008) 103:1320-1. doi:10.1111/j.1572-0241.2007.01782_13.x
55. Brody JD, Ai WZ, Czerwinski DK, Torchia JA, Levy M, Advani RH, et al. In situ vaccination with a TLR9 agonist induces systemic lymphoma regression: a phase I/II study. J Clin Oncol (2010) 28:4324-32. doi:10.1200/JCO.2010.28.9793
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 Biol (2004) 58:862-70. doi:10.1016/j.ijrobp.2003.09.012
57. Postow MA, Callahan MK, Barker CA, Yamada Y, Yuan J, Kitano S, et al. Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med (2012) 366:925-31. doi:10.1056/NEJMoa1112824
58. Stamell EF, Wolchok JD, Gnjatic S, Lee NY, Brownell I. The abscopal effect associated with a systemic anti-melanoma immune response. Int J Radiat Biol (2013) 2:293-5. doi:10.1016/j.ijrobp.2012.03.017
59. Robbins PF, Lu YC, El-Gamil M, Li YF, Gross C, Gartner J, et al. Mining exomic sequencing data to identify mutated antigens recognized by adoptively transferred tumor-reactive T cells. Nat Med (2013) 19:747-52. doi:10.1038/nm.3161
60. de la Cruz-Merino L, Grande-Pulido E, Albero-Tamarit A, Codes-Manuel deVillena ME. Cancer and immune response: old and new evidence for future challenges. Oncologist (2008) 13:1246-54. doi:10.1634/theoncologist.2008-0166
61. Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med (2010) 363:711-23. doi:10.1056/NEJMoa1003466
62. Robert C, Thomas L, Bondarenko I, O'Day S, Weber J, Garbe C, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med (2011) 364:2517-26. doi:10.1056/NEJMoa1104621
63. Dewan MZ, Galloway AE, Kawashima N, Dewyngaert JK, Babb JS, Formenti SC, et al. Fractionated but not single-dose RT induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody. Clin Cancer Res (2009) 15:5379-88. doi:10.1158/1078-0432.CCR-09-0265
64. Gough MJ, Crittenden MR, Sarff M, Pang P, Seung SK, Vetto JT, et al. Adjuvant therapy with agonistic antibodies to CD134 (OX40) increases local control after surgical or radiation therapy of cancer in mic. J Immunother (2010) 33:798-809. doi:10.1097/CJI.0b013e3181ee7095
65. Jensen SM, Maston LD, Gough MJ, Ruby CE, Redmond WL, Crittenden M, et al. Signaling through OX40 enhances antitumor immunity. Semin Oncol (2010) 37:524-32. doi:10.1053/j.seminoncol.2010.09.013
66. 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 Investiga (2014) 124:687-95. doi:10.1172/JCI67313
67. Sabbagh L, Pulle G, Liu Y, Tsitsikov EN, Watts TH. ERK-dependent Bim modulation downstream of the 4-1BB-TRAF1 signaling axis is a critical mediator of CD8 T cell survival in vivo. J Immunol (2008) 180:8093-101.
68. Melero I, Grimaldi AM, Perez-Gracia JL, Ascierto PA. Clinical development of immunostimulatory monoclonal antibodies and opportunities for combination. Clin Cancer Res (2013) 19:997-1008. doi:10.1158/1078-0432.CCR-12-2214
69. Abbas AK, Lichtman AH, Pillai S. Immunity to tumors. In: Abbas AK, Lichtman AH, Pillai S, editors. Cellular and Molecular Immunology. 6th Ed. Philadelphia: Saunders Elsevier (2007). p. 397-417.
70. Ribas A, Butterfield LH, Glaspy JA, Economou JS. Current developments in cancer vaccines and cellular immunotherapy. J Clin Oncol (2003) 21:2415-32. doi:10.1200/JCO.2003.06.041
71. Formenti SC, Friedman K, Chao K, Adams S, Fenton-Kerimian M, Donach ME, et al. Abscopal response in irradiated patients: results of a proof of principle trial. Int J Radiat Oncol (2008) 72:S6-7. doi:10.1016/j.ijrobp.2008.06.782
72. 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
73. Wersäll PJ, Blomgren H, Pisa P, Lax I, Kälkner K-M, Svedman C. Regression of non-irradiated metastases after extracranial stereotactic RT in metastatic renal cell carcinoma. Acta Oncol (2006) 45:493-7. doi:10.1080/02841860600604611
74. Antoniades J, Brady LW, Lightfoot DA. Lymphangiographic demonstration of the abscopal effect in patients with malignant lymphomas. Int J Radiat Oncol (1977) 2:141-7. doi:10.1016/0360-3016(77)90020-7
75. Cotter SE, Dunn GP, Collins KM, Sahni D, Zukotynski KA, Hansen JL, et al. Abscopal effect in a patient with metastatic Merkel cell carcinoma following radiation therapy: potential role of induced antitumor immunity. Arch Dermatol (2001) 147:870-2. doi:10.1001/archdermatol.2011.176