Hypofractionated irradiation has immune stimulatory potential and induces a timely restricted infiltration of immune cells in colon cancer tumors

Frontiers in Immunology

Volumn 8, Issue MAR, 2017, Pages

  Frey, Benjamin ^a   Rückert, Michael ^a   Weber, Julia ^a   Mayr, Xaver ^a   Derer, Anja ^a   Lotter, Michael ^a   Bert, Christoph ^a   Rödel, Franz ^b   Fietkau, Rainer ^a   Gaipl, Udo S ^a  

^a UNIVERSITY HOSPITAL ERLANGEN   (Germany)

^b UNIVERSITY HOSPITAL FRANKFURT   (Germany)

Author keywords

Antigen presenting cells; CD8+ T cell; Colorectal cancer; Hypofractionated radiotherapy; Immunogenic radiotherapy; Macrophages; Tumor cell specific IgM; Tumor infiltrating immune cells

Indexed keywords

B7 ANTIGEN; CD86 ANTIGEN; IMMUNOGLOBULIN M;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; CANCER INFILTRATION; CANCER SURGERY; CANCER SURVIVAL; CD4 LYMPHOCYTE COUNT; CD8+ T LYMPHOCYTE; CELL ACTIVATION; CELL DEATH; CELL MIGRATION; CELL PROLIFERATION; CFU COUNTING; COLON CANCER; DENDRITIC CELL; FLOW CYTOMETRY; HYPOFRACTIONATED RADIOTHERAPY; IMMUNE RESPONSE; IMMUNOSTIMULATION; IRRADIATION; MOUSE; NONHUMAN; TUMOR GROWTH; TUMOR MICROENVIRONMENT;

EID: 85017277731     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2017.00231     Document Type: Article

References (41)

1. 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
2. Sharma RA, Plummer R, Stock JK, Greenhalgh TA, Ataman O, Kelly S, et al. Clinical development of new drug-radiotherapy combinations. Nat Rev Clin Oncol (2016) 13(10):627-42. doi:10.1038/nrclinonc.2016.79
3. Lucarini V, Buccione C, Ziccheddu G, Peschiaroli F, Sestili P, Puglisi R, et al. Combining type I interferons and 5-Aza-2'-deoxycitidine to improve anti-tumor response against melanoma. J Invest Dermatol (2016) 137(1):159-69. doi:10.1016/j.jid.2016.08.024
4. Minnar CM, Murphy WJ. Immunoregulatory pathways following strong inflammatory processes markedly impair CD4+ T cell responses. Hum Vaccin Immunother (2016) 12(9):2249-52. doi:10.1080/21645515.2016.1174357
5. Atun R, Jaffray DA, Barton MB, Bray F, Baumann M, Vikram B, et al. Expanding global access to radiotherapy. Lancet Oncol (2015) 16(10):1153-86. doi:10.1016/s1470-2045(15)00222-3
6. 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
7. 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
8. Popp I, Grosu AL, Niedermann G, Duda DG. Immune modulation by hypofractionated stereotactic radiation therapy: therapeutic implications. Radiother Oncol (2016) 120(2):185-94. doi:10.1016/j.radonc.2016.07.013
9. Mole RH. Whole body irradiation; radiobiology or medicine? Br J Radiol (1953) 26(305):234-41. doi:10.1259/0007-1285-26-305-234
10. 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
11. Wattenberg MM, Fahim A, Ahmed MM, Hodge JW. Unlocking the combination: potentiation of radiation-induced antitumor responses with immunotherapy. Radiat Res (2014) 182(2):126-38. doi:10.1667/rr13374.1
12. Frey B, Rubner Y, Kulzer L, Werthmoller N, Weiss EM, Fietkau R, et al. Antitumor immune responses induced by ionizing irradiation and further immune stimulation. Cancer Immunol Immunother (2014) 63(1):29-36. doi:10.1007/s00262-013-1474-y
13. Gameiro SR, Jammeh ML, Wattenberg MM, Tsang KY, Ferrone S, Hodge JW. Radiation-induced immunogenic modulation of tumor enhances antigen processing and calreticulin exposure, resulting in enhanced T-cell killing. Oncotarget (2014) 5(2):403-16. doi:10.18632/oncotarget.1719
14. Lim JY, Gerber SA, Murphy SP, Lord EM. Type I interferons induced by radiation therapy mediate recruitment and effector function of CD8(+) T cells. Cancer Immunol Immunother (2014) 63(3):259-71. doi:10.1007/s00262-013-1506-7
15. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin (2015) 65(1):5-29. doi:10.3322/caac.21254
16. Young KH, Newell P, Cottam B, Friedman D, Savage T, Baird JR, et al. TGFbeta inhibition prior to hypofractionated radiation enhances efficacy in preclinical models. Cancer Immunol Res (2014) 2(10):1011-22. doi:10.1158/2326-6066.cir-13-0207
17. Vassileva V, Rajkumar V, Mazzantini M, Robson M, Badar A, Sharma S, et al. Significant therapeutic efficacy with combined radioimmunotherapy and cetuximab in preclinical models of colorectal cancer. J Nucl Med (2015) 56(8):1239-45. doi:10.2967/jnumed.115.157362
18. Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science (2006) 313(5795):1960-4. doi:10.1126/science.1129139
19. Lerner WA, Pearlstein E, Ambrogio C, Karpatkin S. A new mechanism for tumor induced platelet aggregation. Comparison with mechanisms shared by other tumor with possible pharmacologic strategy toward prevention of metastases. Int J Cancer (1983) 31(4):463-9. doi:10.1002/ijc.2910310411
20. Wang S, Campos J, Gallotta M, Gong M, Crain C, Naik E, et al. Intratumoral injection of a CpG oligonucleotide reverts resistance to PD-1 blockade by expanding multifunctional CD8+ T cells. Proc Natl Acad Sci U S A (2016) 113(46):E7240-9. doi:10.1073/pnas.1608555113
21. Lutz MB, Kukutsch N, Ogilvie AL, Rossner S, Koch F, Romani N, et al. An advanced culture method for generating large quantities of highly pure dendritic cells from mouse bone marrow. J Immunol Methods (1999) 223(1):77-92. doi:10.1016/S0022-1759(98)00204-X
22. Euhus DM, Hudd C, LaRegina MC, Johnson FE. Tumor measurement in the nude mouse. J Surg Oncol (1986) 31(4):229-34. doi:10.1002/jso.2930310402
23. Werthmoller N, Frey B, Ruckert M, Lotter M, Fietkau R, Gaipl US. Combination of ionising radiation with hyperthermia increases the immunogenic potential of B16-F10 melanoma cells in vitro and in vivo. Int J Hyperthermia (2016) 32(1):23-30. doi:10.3109/02656736.2015.1106011
24. Shinto E, Hase K, Hashiguchi Y, Sekizawa A, Ueno H, Shikina A, et al. CD8+ and FOXP3+ tumor-infiltrating T cells before and after chemoradiotherapy for rectal cancer. Ann Surg Oncol (2014) 21(Suppl 3):S414-21. doi:10.1245/s10434-014-3584-y
25. Perez-Ruiz E, Berraondo P. Immunological landscape and clinical management of rectal cancer. Front Immunol (2016) 7:61. doi:10.3389/fimmu.2016.00061
26. Galon J, Pages F, Marincola FM, Angell HK, Thurin M, Lugli A, et al. Cancer classification using the immunoscore: a worldwide task force. J Transl Med (2012) 10:205. doi:10.1186/1479-5876-10-205
27. Bindea G, Mlecnik B, Tosolini M, Kirilovsky A, Waldner M, Obenauf AC, et al. Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer. Immunity (2013) 39(4):782-95. doi:10.1016/j.immuni.2013.10.003
28. Deloch L, Derer A, Hartmann J, Frey B, Fietkau R, Gaipl US. Modern radiotherapy concepts and the impact of radiation on immune activation. Front Oncol (2016) 6:141. doi:10.3389/fonc.2016.00141
29. Ma Y, Adjemian S, Mattarollo SR, Yamazaki T, Aymeric L, Yang H, et al. Anticancer chemotherapy-induced intratumoral recruitment and differentiation of antigen-presenting cells. Immunity (2013) 38(4):729-41. doi:10.1016/j.immuni.2013.03.003
30. Schildkopf P, Frey B, Ott OJ, Rubner Y, Multhoff G, Sauer R, et al. Radiation combined with hyperthermia induces HSP70-dependent maturation of dendritic cells and release of pro-inflammatory cytokines by dendritic cells and macrophages. Radiother Oncol (2011) 101(1):109-15. doi:10.1016/j.radonc.2011.05.056
31. 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(5):589-602. doi:10.1016/j.ccr.2013.09.014
32. Hettich M, Lahoti J, Prasad S, Niedermann G. Checkpoint antibodies but not T cell-recruiting diabodies effectively synergize with TIL-inducing gamma-irradiation. Cancer Res (2016) 76(16):4673-83. doi:10.1158/0008-5472.can-15-3451
33. Bernstein MB, Krishnan S, Hodge JW, Chang JY. Immunotherapy and stereotactic ablative radiotherapy (ISABR): a curative approach? Nat Rev Clin Oncol (2016) 13(8):516-24. doi:10.1038/nrclinonc.2016.30
34. Deperas-Kaminska M, Bajinskis A, Marczyk M, Polanska J, Wersall P, Lidbrink E, et al. Radiation-induced changes in levels of selected proteins in peripheral blood serum of breast cancer patients as a potential triage biodosimeter for large-scale radiological emergencies. Health Phys (2014) 107(6):555-63. doi:10.1097/hp.0000000000000158
35. 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
36. Heylmann D, Rodel F, Kindler T, Kaina B. Radiation sensitivity of human and murine peripheral blood lymphocytes, stem and progenitor cells. Biochim Biophys Acta (2014) 1846(1):121-9. doi:10.1016/j.bbcan.2014.04.009
37. Sharabi AB, Lim M, DeWeese TL, Drake CG. Radiation and checkpoint blockade immunotherapy: radiosensitisation and potential mechanisms of synergy. Lancet Oncol (2015) 16(13):e498-509. doi:10.1016/s1470-2045(15)00007-8
38. Huang J, Wang Y, Guo J, Lu H, Lin X, Ma L, et al. Radiation-induced apoptosis along with local and systemic cytokine elaboration is associated with DC plus radiotherapy-mediated renal cell tumor regression. Clin Immunol (2007) 123(3):298-310. doi:10.1016/j.clim.2007.02.005
39. Habets TH, Oth T, Houben AW, Huijskens MJ, Senden-Gijsbers BL, Schnijderberg MC, et al. Fractionated radiotherapy with 3 x 8 Gy induces systemic anti-tumour responses and abscopal tumour inhibition without modulating the humoral anti-tumour response. PLoS One (2016) 11(7):e0159515. doi:10.1371/journal.pone.0159515
40. Ruhle PF, Fietkau R, Gaipl US, Frey B. Development of a modular assay for detailed immunophenotyping of peripheral human whole blood samples by multicolor flow cytometry. Int J Mol Sci (2016) 17(8):ii:E1316. doi:10.3390/ijms17081316
41. Baues C, Semrau R, Gaipl US, Brockelmann PJ, Rosenbrock J, Engert A, et al. Checkpoint inhibitors and radiation treatment in Hodgkin's lymphoma: new study concepts of the German Hodgkin Study Group. Strahlenther Onkol (2016) 193(2):95-9. doi:10.1007/s00066-016-1050-4