Combining radiotherapy with immunotherapy

Combining radiotherapy with immunotherapy

It has long been known that radiation destroys the tumorsby killing cells. However, immunotherapy is developingrapidly, combination of immunotherapy with chemotherapyand radiotherapy seems to be a viable option. Preclinicalstudies combining immunotherapy with radiotherapyresulted in promising data, where manipulating immuneresponse enhances the effects of radiation. There are manyways of immunotherapy-radiotherapy combination, and thefield is open for clinical research. This paper reviews thecurrent situation on this topic.Keywords: Immunotherapy, Radiotherapy

___

  • 1. Kamrava M, Bernstein MB, Camphausen K, Hodge JW. Combining radiation, immunotherapy, and antiangiogenesis agents in the management of cancer: the Three Musketeers or just another quixotic combination? Mol Biosyst 2009;5:1262-70. doi: 10.1039/b911313b.
  • 2. 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.
  • 3. Barker CA, Postow MA. Combinations of radiation therapy and immunotherapy for melanoma: a review of clinical outcomes. Int J Radiat Oncol Biol Phys 2014;88:986-97. doi: 10.1016/j.ijrobp.2013.08.035.
  • 4. Shahabi V, Postow MA, Tuck D, Wolchok JD. Immunepriming of the tumor microenvironment by radiotherapy: rationale for combination with immunotherapy to improve anticancer efficacy. Am J Clin Oncol 2015;38:90-7. doi : 10.1097/COC.0b013e3182868ec8.
  • 5. Sharon E, Polley MY, Bernstein MB, Ahmed M. Immunotherapy and radiation therapy: considerations for successfully combining radiation into the paradigm of immuno-oncology drug development. Radiat Res 2014;182:252-7. doi: 10.1667/RR13707.1.
  • 6. Kalbasi A, June CH, Haas N, Vapiwala N. Radiation and immunotherapy: a synergistic combination. J Clin Invest 2013;123:2756-63. doi: 10.1172/JCI69219.
  • 7. Golden EB, Pellicciotta I, Demaria S, Barcellos-Hoff MH, Formenti SC. The convergence of radiation and immunogenic cell death signaling pathways. Front Oncol 2012;2:88. doi: 10.3389/fonc.2012.00088.
  • 8. Srivastava P. Roles of heat-shock proteins in innate and adaptive immunity. Nat Rev Immunol 2002;2:185-94. doi:10.1038/nri749
  • 9. Ogden CA, deCathelineau A, Hoffmann PR, et al. C1q and mannose binding lectin engagement of cell surface calreticulin and CD91 initiates macropinocytosis and uptake of apoptotic cells. J Exp Med 2001;194:781-95. doi:10.1084/jem.194.6.781.
  • 10. Formenti SC, Demaria S. Combining radiotherapy and cancer immunotherapy: a paradigm shift. J Natl Cancer Inst 2013;105:256-65. doi:10.1093/jnci/djs629.
  • 11. Golden EB, Frances D, Pellicciotta I, Demaria S, Barcellos-Hoff MH, Formenti SC. Radiation fosters dose-dependent and chemotherapy-induced immunogenic cell death. Oncoimmunology 2014;3:e28518. doi:10.4161/onci.28518.
  • 12. Gaugler MH, Squiban C, van der Meeren A, Bertho JM, Vandamme M, Mouthon MA. Late and persistent upregulation of intercellular adhesion molecule-1 (ICAM- 1) expression by ionizing radiation in human endothelial cells in vitro. Int J Radiat Biol 1997;72:201-9.
  • 13. Matsumura S, Wang B, Kawashima N, et al. Radiationinduced CXCL16 release by breast cancer cells attracts effector T cells. J Immunol 2008;181:3099-107.
  • 14. Rekers NH, Troost EG, Zegers CM, Germeraad WT, Dubois LJ, Lambin P. Stereotactic ablative body radiotherapy combined with immunotherapy: present status and future perspectives. Cancer Radiother 2014;18:391-5. doi:10.1016/j.canrad.2014.06.012.
  • 15. Formenti SC, Demaria S. Systemic effects of local radiotherapy. Lancet Oncol 2009; 10:718-26. doi: 10.1016/S1470-2045(09)70082-8.
  • 16. DewanMZ, GallowayAE, KawashimaN, et al. Fractionated but not single-dose radiotherapy induces an immune- mediated abscopal effect when combined with anti-CTLA-4antibody. Clin Cancer Res 2009; 15:5379–88. doi: 10.1158/1078-0432.
  • 17. Postow MA, Callahan MK, Barker CA, 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.
  • 18. Golden EB, Demaria S, Schiff PB, Chachoua A, Formenti SC. An abscopal response to radiation andipilimumab in a patient with metastatic non-small cell lung cancer. Cancer Immunol Res 2013;1:365–72. doi: 10.1158/2326-6066
  • 19. Ehlers G, Fridman M. Abscopal effect of radiation in papillary adenocarcinoma. Br J Radiol 1973;46:220–2.
  • 20. Rees GJ, Ross CM. Abscopal regression following radiotherapy for adenocarcinoma. Br J Radiol 1983; 56:63–6.
  • 21. Ohba K, Omagari K, Nakamura T, et al. Abscopal regression of hepatocellular carcinoma after radiotherapy for bone metastasis. Gut 1998;43:575–7.