Radiation Oncology Journal

The Korean Society for Radiation Oncology (대한방사선종양학회)
권호 표지
DOI QR코드

DOI QR Code

Radiotherapy and immune checkpoint blockades: a snapshot in 2016

  • Koo, Taeryool (Department of Radiation Oncology, Hallym University Chuncheon Sacred Heart Hospital) ;
  • Kim, In Ah (Department of Radiation Oncology, Seoul National University College of Medicine)
  • Received : 2016.11.14
  • Accepted : 2016.12.13
  • Published : 2016.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Immune checkpoint blockades including monoclonal antibodies (mAbs) of cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1), and programmed death-ligand 1 (PD-L1) have been emerged as a promising anticancer therapy. Several immune checkpoint blockades have been approved by US Food and Drug Administration (FDA), and have shown notable success in clinical trials for patients with advanced melanoma and non-small cell lung cancer. Radiotherapy is a promising combination partner of immune checkpoint blockades due to its potent pro-immune effect. This review will cover the current issue and the future perspectives for combined with radiotherapy and immune checkpoint blockades based upon the available preclinical and clinical data.

Keywords

References

  1. Formenti SC, Demaria S. Combining radiotherapy and cancer immunotherapy: a paradigm shift. J Natl Cancer Inst 2013;105:256-65. https://doi.org/10.1093/jnci/djs629
  2. Reits EA, Hodge JW, Herberts CA, et al. Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy. J Exp Med 2006;203:1259-71. https://doi.org/10.1084/jem.20052494
  3. Gupta A, Probst HC, Vuong V, et al. Radiotherapy promotes tumor-specific effector CD8+ T cells via dendritic cell activation. J Immunol 2012;189:558-66. https://doi.org/10.4049/jimmunol.1200563
  4. 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. https://doi.org/10.4049/jimmunol.174.12.7516
  5. Siva S, MacManus MP, Martin RF, Martin OA. Abscopal effects of radiation therapy: a clinical review for the radiobiologist. Cancer Lett 2015;356:82-90. https://doi.org/10.1016/j.canlet.2013.09.018
  6. Lenschow DJ, Walunas TL, Bluestone JA. CD28/B7 system of T cell costimulation. Annu Rev Immunol 1996;14:233-58. https://doi.org/10.1146/annurev.immunol.14.1.233
  7. Sansom DM. CD28, CTLA-4 and their ligands: who does what and to whom? Immunology 2000;101:169-77. https://doi.org/10.1046/j.1365-2567.2000.00121.x
  8. Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol 2008;26:677-704. https://doi.org/10.1146/annurev.immunol.26.021607.090331
  9. Hodi FS, O'Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010;363:711-23. https://doi.org/10.1056/NEJMoa1003466
  10. Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 2011;364:2517-26. https://doi.org/10.1056/NEJMoa1104621
  11. Maio M, Grob JJ, Aamdal S, et al. Five-year survival rates for treatment-naive patients with advanced melanoma who received ipilimumab plus dacarbazine in a phase III trial. J Clin Oncol 2015;33:1191-6. https://doi.org/10.1200/JCO.2014.56.6018
  12. Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 2015;373:23-34. https://doi.org/10.1056/NEJMoa1504030
  13. Robert C, Schachter J, Long GV, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 2015;372:2521-32. https://doi.org/10.1056/NEJMoa1503093
  14. Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 2015;373:123-35. https://doi.org/10.1056/NEJMoa1504627
  15. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 2015;373:1627-39. https://doi.org/10.1056/NEJMoa1507643
  16. Herbst RS, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 2016;387:1540-50. https://doi.org/10.1016/S0140-6736(15)01281-7
  17. Ribas A, Hamid O, Daud A, et al. Association of pembrolizumab with tumor response and survival among patients with advanced melanoma. JAMA 2016;315:1600-9. https://doi.org/10.1001/jama.2016.4059
  18. Ribas A, Puzanov I, Dummer R, et al. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. Lancet Oncol 2015;16:908-18. https://doi.org/10.1016/S1470-2045(15)00083-2
  19. Patnaik A, Kang SP, Rasco D, et al. Phase I study of pembrolizumab (MK-3475; Anti-PD-1 monoclonal antibody) in patients with advanced solid tumors. Clin Cancer Res 2015;21:4286-93. https://doi.org/10.1158/1078-0432.CCR-14-2607
  20. Royal RE, Levy C, Turner K, et al. Phase 2 trial of single agent Ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma. J Immunother 2010;33:828-33. https://doi.org/10.1097/CJI.0b013e3181eec14c
  21. Kachikwu EL, Iwamoto KS, Liao YP, et al. Radiation enhances regulatory T cell representation. Int J Radiat Oncol Biol Phys 2011;81:1128-35. https://doi.org/10.1016/j.ijrobp.2010.09.034
  22. Wing K, Onishi Y, Prieto-Martin P, et al. CTLA-4 control over Foxp3+ regulatory T cell function. Science 2008;322:271-5. https://doi.org/10.1126/science.1160062
  23. Demaria S, Kawashima N, Yang AM, et al. Immune-mediated inhibition of metastases after treatment with local radiation and CTLA-4 blockade in a mouse model of breast cancer. Clin Cancer Res 2005;11(2 Pt 1):728-34.
  24. Wu L, Wu MO, De la Maza L, et al. Targeting the inhibitory receptor CTLA-4 on T cells increased abscopal effects in murine mesothelioma model. Oncotarget 2015;6:12468-80. https://doi.org/10.18632/oncotarget.3487
  25. Yoshimoto Y, Suzuki Y, Mimura K, et al. Radiotherapy-induced anti-tumor immunity contributes to the therapeutic efficacy of irradiation and can be augmented by CTLA-4 blockade in a mouse model. PLoS One 2014;9:e92572. https://doi.org/10.1371/journal.pone.0092572
  26. Liang H, Deng L, Chmura S, et al. Radiation-induced equilibrium is a balance between tumor cell proliferation and T cell-mediated killing. J Immunol 2013;190:5874-81. https://doi.org/10.4049/jimmunol.1202612
  27. Twyman-Saint Victor C, Rech AJ, Maity A, et al. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature 2015;520:373-7. https://doi.org/10.1038/nature14292
  28. Deng L, Liang H, Burnette B, et al. Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. J Clin Invest 2014;124:687-95. https://doi.org/10.1172/JCI67313
  29. Vanpouille-Box C, Diamond JM, Pilones KA, et al. $TGF{\beta}$ is a master regulator of radiation therapy-induced antitumor immunity. Cancer Res 2015;75:2232-42. https://doi.org/10.1158/0008-5472.CAN-14-3511
  30. Pilon-Thomas S, Mackay A, Vohra N, Mule JJ. Blockade of programmed death ligand 1 enhances the therapeutic efficacy of combination immunotherapy against melanoma. J Immunol 2010;184:3442-9. https://doi.org/10.4049/jimmunol.0904114
  31. Sharabi AB, Nirschl CJ, Kochel CM, et al. Stereotactic radiation therapy augments antigen-specific PD-1-mediated antitumor immune responses via cross-presentation of tumor antigen. Cancer Immunol Res 2015;3:345-55. https://doi.org/10.1158/2326-6066.CIR-14-0196
  32. Park SS, Dong H, Liu X, et al. PD-1 restrains radiotherapy-induced abscopal effect. Cancer Immunol Res 2015;3:610-9. https://doi.org/10.1158/2326-6066.CIR-14-0138
  33. Zeng J, See AP, Phallen J, et al. Anti-PD-1 blockade and stereotactic radiation produce long-term survival in mice with intracranial gliomas. Int J Radiat Oncol Biol Phys 2013;86:343-9. https://doi.org/10.1016/j.ijrobp.2012.12.025
  34. Slovin SF, Higano CS, Hamid O, et al. Ipilimumab alone or in combination with radiotherapy in metastatic castration-resistant prostate cancer: results from an open-label, multicenter phase I/II study. Ann Oncol. 2013;24:1813-21. https://doi.org/10.1093/annonc/mdt107
  35. Kwon ED, Drake CG, Scher HI, et al. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol 2014;15:700-12. https://doi.org/10.1016/S1470-2045(14)70189-5
  36. Barker CA, Postow MA, Khan SA, et al. Concurrent radiotherapy and ipilimumab immunotherapy for patients with melanoma. Cancer Immunol Res 2013;1:92-8. https://doi.org/10.1158/2326-6066.CIR-13-0082
  37. 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. https://doi.org/10.1056/NEJMoa1112824
  38. Golden EB, Demaria S, Schiff PB, Chachoua A, Formenti SC. An abscopal response to radiation and ipilimumab in a patient with metastatic non-small cell lung cancer. Cancer Immunol Res 2013;1:365-72. https://doi.org/10.1158/2326-6066.CIR-13-0115
  39. Knisely JP, Yu JB, Flanigan J, Sznol M, Kluger HM, Chiang VL. Radiosurgery for melanoma brain metastases in the ipilimumab era and the possibility of longer survival. J Neurosurg 2012;117:227-33. https://doi.org/10.3171/2012.5.JNS111929
  40. Gerber NK, Young RJ, Barker CA, et al. Ipilimumab and whole brain radiation therapy for melanoma brain metastases. J Neurooncol 2015;121:159-65. https://doi.org/10.1007/s11060-014-1617-9
  41. Silk AW, Bassetti MF, West BT, Tsien CI, Lao CD. Ipilimumab and radiation therapy for melanoma brain metastases. Cancer Med 2013;2:899-906. https://doi.org/10.1002/cam4.140
  42. Lee Y, Auh SL, Wang 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. https://doi.org/10.1182/blood-2009-02-206870
  43. Dovedi SJ, Adlard AL, Lipowska-Bhalla G, et al. Acquired resistance to fractionated radiotherapy can be overcome by concurrent PD-L1 blockade. Cancer Res 2014;74:5458-68. https://doi.org/10.1158/0008-5472.CAN-14-1258
  44. Bernstein MB, Garnett CT, Zhang H, et al. Radiation-induced modulation of costimulatory and coinhibitory T-cell signaling molecules on human prostate carcinoma cells promotes productive antitumor immune interactions. Cancer Biother Radiopharm 2014;29:153-61. https://doi.org/10.1089/cbr.2013.1578
  45. Dewan MZ, Galloway AE, Kawashima N, 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;15:5379-88. https://doi.org/10.1158/1078-0432.CCR-09-0265
  46. Kiess AP, Wolchok JD, Barker CA, et al. Stereotactic radiosurgery for melanoma brain metastases in patients receiving ipilimumab: safety profile and efficacy of combined treatment. Int J Radiat Oncol Biol Phys 2015;92:368-75. https://doi.org/10.1016/j.ijrobp.2015.01.004
  47. Lutz ER, Wu AA, Bigelow E, et al. Immunotherapy converts nonimmunogenic pancreatic tumors into immunogenic foci of immune regulation. Cancer Immunol Res 2014;2:616-31. https://doi.org/10.1158/2326-6066.CIR-14-0027
  48. Stagg J, Allard B. Immunotherapeutic approaches in triple-negative breast cancer: latest research and clinical prospects. Ther Adv Med Oncol 2013;5:169-81. https://doi.org/10.1177/1758834012475152
  49. Lim SH, Hong M, Ahn S, et al. Changes in tumour expression of programmed death-ligand 1 after neoadjuvant concurrent chemoradiotherapy in patients with squamous oesophageal cancer. Eur J Cancer 2016;52:1-9. https://doi.org/10.1016/j.ejca.2015.09.019
  50. Hecht M, Buttner-Herold M, Erlenbach-Wunsch K, et al. PD-L1 is upregulated by radiochemotherapy in rectal adenocarcinoma patients and associated with a favourable prognosis. Eur J Cancer 2016;65:52-60. https://doi.org/10.1016/j.ejca.2016.06.015

Cited by

  1. Mechanism of the Antitumor and Radiosensitizing Effects of a Manganese Porphyrin, MnHex-2-PyP vol.27, pp.14, 2016, https://doi.org/10.1089/ars.2016.6889
  2. Intravenous dendritic cell administration enhances suppression of lung metastasis induced by carbon-ion irradiation vol.58, pp.4, 2016, https://doi.org/10.1093/jrr/rrx005
  3. Short review of potential synergies of immune checkpoint inhibition and radiotherapy with a focus on Hodgkin lymphoma: radio-immunotherapy opens new doors vol.9, pp.5, 2017, https://doi.org/10.2217/imt-2017-0002
  4. The future of immune checkpoint cancer therapy after PD-1 and CTLA-4 vol.9, pp.8, 2016, https://doi.org/10.2217/imt-2017-0024
  5. Efficacy of combined hypo-fractionated radiotherapy and anti-PD-1 monotherapy in difficult-to-treat advanced melanoma patients vol.7, pp.7, 2016, https://doi.org/10.1080/2162402x.2018.1442166
  6. Combining radiotherapy and ipilimumab induces clinically relevant radiation-induced abscopal effects in metastatic melanoma patients: A systematic review vol.9, pp.None, 2018, https://doi.org/10.1016/j.ctro.2017.12.004
  7. Novel biological strategies to enhance the radiation therapeutic ratio vol.36, pp.3, 2016, https://doi.org/10.3857/roj.2018.00332
  8. Combined radiotherapy with nivolumab for extracranial metastatic malignant melanoma vol.36, pp.12, 2018, https://doi.org/10.1007/s11604-018-0774-8
  9. Combination Treatment of Stereotactic Body Radiation Therapy and Immature Dendritic Cell Vaccination for Augmentation of Local and Systemic Effects vol.51, pp.2, 2016, https://doi.org/10.4143/crt.2018.186
  10. Metabolic Reprogramming in the Tumor Microenvironment With Immunocytes and Immune Checkpoints vol.11, pp.None, 2021, https://doi.org/10.3389/fonc.2021.759015
  11. Potential and unsolved problems of anti-PD-1/PD-L1 therapy combined with radiotherapy vol.107, pp.4, 2016, https://doi.org/10.1177/0300891620940382