Radiation and Immune Checkpoint Blockade: From Bench to Clinic

Seminars in Radiation Oncology

Volumn 27, Issue 3, 2017, Pages 289-298

  Shabason, Jacob E ^a   Minn, Andy J ^a,b  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4 ANTIBODY; IPILIMUMAB; PD L1 ANTIBODY; UNCLASSIFIED DRUG;

CANCER IMMUNOTHERAPY; CANCER RADIOTHERAPY; CLINICAL EFFECTIVENESS; HUMAN; IMMUNE CHECKPOINT BLOCKADE; IMMUNOSTIMULATION; IMMUNOSUPPRESSIVE TREATMENT; MALIGNANT NEOPLASM; OUTCOME ASSESSMENT; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PHASE 4 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; RADIATION DOSE FRACTIONATION; REVIEW; TUMOR ESCAPE; TUMOR IMMUNITY; IMMUNOLOGY; IMMUNOTHERAPY; METASTASIS; MULTIMODALITY CANCER THERAPY; NEOPLASM; PROCEDURES;

COMBINED MODALITY THERAPY; HUMANS; IMMUNOTHERAPY; NEOPLASM METASTASIS; NEOPLASMS; TUMOR ESCAPE;

EID: 85018246561     PISSN: 10534296     EISSN: 15329461     Source Type: Journal    
DOI: 10.1016/j.semradonc.2017.03.002     Document Type: Review

References (68)

1. Hanahan, D., Weinberg, R.A., Hallmarks of cancer: The next generation. Cell 144:5 (2011), 646–674.
2. Topalian, S.L., Drake, C.G., Pardoll, D.M., Immune checkpoint blockade: A common denominator approach to cancer therapy. Cancer Cell 27:4 (2015), 450–461.
3. Hodi, F.S., O'Day, SJ., McDermott, D.F., et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363:8 (2010), 711–723.
4. Schadendorf, D., Hodi, FS., Robert, C., et al. Pooled analysis of long-term survival data from phase II and phase III trials of ipilimumab in unresectable or metastatic melanoma. J Clin Oncol 33:17 (2015), 1889–1894.
5. Hodi FS, Sznol M, Carvajal R, et al: Durable, long-term survival in previously treated patients with advanced melanoma (MEL) who received nivolumab (NIVO) monotherapy in a phase I trial. AACR Annual Meeting. Abstract CT001; 2016. Presented April 17, 2016.
6. Robert, C., Ribas, A., Hamid, O., et al. Three-year overall survival for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. J Clin Oncol, 34(suppl), 2016 [abstract 9503].
7. Borghaei, H., Paz-Ares, L., Horn, L., et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 373:17 (2015), 1627–1639.
8. Brahmer, J., Reckamp, KL., Baas, P., et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 373:2 (2015), 123–135.
9. Garon, E.B., Rizvi, NA., Huli, R., et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 372:21 (2015), 2018–2028.
10. Antonia, S.J., Lopez-Martin, JA., Bendell, J., et al. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): A multicentre, open-label, phase 1/2 trial. Lancet Oncol 17:7 (2016), 883–895.
11. Motzer, R.J., Escudier, B., McDermott, DF., et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med 373:19 (2015), 1803–1813.
12. Ansell, S.M., Lesokhin, AM., Borrello, I., et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin׳s lymphoma. N Engl J Med 372:4 (2015), 311–319.
13. Nghiem, P.T., Bhatia, S., Lipson, EJ., et al. PD-1 blockade with pembrolizumab in advanced merkel-cell carcinoma. N Engl J Med 374:26 (2016), 2542–2552.
14. Rosenberg, J.E., Hoffman-Censits, J., Powles, T., et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: A single-arm, multicentre, phase 2 trial. Lancet 387:10031 (2016), 1909–1920.
15. Nanda, R., Chow, LQ., Dees, EC., et al. Pembrolizumab in patients with advanced triple-negative breast cancer: Phase Ib KEYNOTE-012 study. J Clin Oncol 34:21 (2016), 2460–2467.
16. Hamanishi, J., Mandai, M., Ikeda, T., et al. Safety and antitumor activity of anti-PD-1 antibody, nivolumab, in patients with platinum-resistant ovarian cancer. J Clin Oncol 33:34 (2015), 4015–4022.
17. Muro, K., Chung, HC., Shankaran, V., et al. Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): A multicentre, open-label, phase 1b trial. Lancet Oncol 17:6 (2016), 717–726.
18. Seiwert, T.Y., Burtness, B., Mehra, R., et al. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): An open-label, multicentre, phase 1b trial. Lancet Oncol 17:7 (2016), 956–965.
19. Siva, S., MacManus, MP., Martin, RF., et al. Abscopal effects of radiation therapy: A clinical review for the radiobiologist. Cancer Lett 356:1 (2015), 82–90.
20. Chakravarty, P.K., Alfieri, A., Thomas, E.K., et al. Flt3-ligand administration after radiation therapy prolongs survival in a murine model of metastatic lung cancer. Cancer Res 59:24 (1999), 6028–6032.
21. Demaria, S., Kawashima, N., Yang, A.M., 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 11:2 Pt 1 (2005), 728–734.
22. Dewan, M.Z., Galloway, A.E., 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 15:17 (2009), 5379–5388.
23. 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 114:3 (2009), 589–595.
24. Reits, E.A., Hodge, J.W., Herberts, C.A., et al. Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy. J Exp Med 203:5 (2006), 1259–1271.
25. Sharma, A., Bode, B., Studer, G., et al. Radiotherapy of human sarcoma promotes an intratumoral immune effector signature. Clin Cancer Res 19:17 (2013), 4843–4853.
26. Sharma, A., Bode, B., Wenger, R.H., et al. Gamma-radiation promotes immunological recognition of cancer cells through increased expression of cancer-testis antigens in vitro and in vivo. PLoS One, 6(11), 2011, e28217.
27. Twyman-Saint Victor, C., Rech, A.J., Maity, A., et al. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature 520:7547 (2015), 373–377.
28. Rizvi, N.A., Hellmann, MD., Snyder, A., et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348:6230 (2015), 124–128.
29. Kroemer, G., Galluzzi, L., Kepp, O., et al. Immunogenic cell death in cancer therapy. Annu Rev Immunol 31 (2013), 51–72.
30. Minn, A.J., Interferons and the immunogenic effects of cancer therapy. Trends Immunol 36:11 (2015), 725–737.
31. Sistigu, A., Yamazaki, T., Vaccheli, E., et al. Cancer cell-autonomous contribution of type I interferon signaling to the efficacy of chemotherapy. Nat Med 20:11 (2014), 1301–1309.
32. Chiappinelli, K.B., Strissel, P.L, Desrichard, A., et al. Inhibiting DNA methylation causes an interferon response in cancer via dsRNA including endogenous retroviruses. Cell 162:5 (2015), 974–986.
33. Ganss, R., Ryschich, E., Klar, E., et al. Combination of T-cell therapy and trigger of inflammation induces remodeling of the vasculature and tumor eradication. Cancer Res 62:5 (2002), 1462–1470.
34. Klug, F., Prakash, H., Huber, PE., et al. Low-dose irradiation programs macrophage differentiation to an iNOS(+)/M1 phenotype that orchestrates effective T cell immunotherapy. Cancer Cell 24:5 (2013), 589–602.
35. Price, J.G., Idoyaga, J., Salmon, H., et al. CDKN1A regulates Langerhans cell survival and promotes Treg cell generation upon exposure to ionizing irradiation. Nat Immunol 16:10 (2015), 1060–1068.
36. Deng, L., Liang, H., Burnette, B., et al. Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. J Clin Invest 124:2 (2014), 687–695.
37. Xu, J., Escamila, J., Mok, S., et al. CSF1R signaling blockade stanches tumor-infiltrating myeloid cells and improves the efficacy of radiotherapy in prostate cancer. Cancer Res 73:9 (2013), 2782–2794.
38. Yamazaki, H., Nishiyama, K., Tanaka, E., et al. Radiotherapy for early glottic carcinoma (T1N0M0): Results of prospective randomized study of radiation fraction size and overall treatment time. Int J Radiat Oncol Biol Phys 64:1 (2006), 77–82.
39. Timmerman, R., Paulus, R., Galvin, J., et al. Stereotactic body radiation therapy for inoperable early stage lung cancer. J Am Med Assoc 303:11 (2010), 1070–1076.
40. Tsai, M.H., Cook, JA., Chandramouli, GV., et al. Gene expression profiling of breast, prostate, and glioma cells following single versus fractionated doses of radiation. Cancer Res 67:8 (2007), 3845–3852.
41. Srivastava, R.M., Clump, DA., Ferris, RL., Anti-PD-1 mAb pre-radiotherapy (RT) loading dose and fractionated RT induce better tumor-specific immunity and tumor shrinkage than sequential administration in an HPV+ head and neck cancer model. J Immunother Cancer, 3(suppl 2), 2015, 314.
42. Chandra, R.A., wilhit, TJ., Balboni, TA., et al. A systematic evaluation of abscopal responses following radiotherapy in patients with metastatic melanoma treated with ipilimumab. Oncoimmunology, 4(11), 2015, e1046028.
43. Sridharan, V., Margalit, DN., Lynch, SA., et al. Definitive chemoradiation alters the immunologic landscape and immune checkpoints in head and neck cancer. Br J Cancer 115:2 (2016), 252–260.
44. Golden, E.B., Chhabra, A., Chachoua, A., 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 16:7 (2015), 795–803.
45. Lugade, A.A., Moran, JP., Gerber, SA., et al. Local radiation therapy of B16 melanoma tumors increases the generation of tumor antigen-specific effector cells that traffic to the tumor. J Immunol 174:12 (2005), 7516–7523.
46. Filatenkov, A., Baker, J., Mueller, AM., et al. Ablative tumor radiation can change the tumor immune cell microenvironment to induce durable complete remissions. Clin Cancer Res 21:16 (2015), 3727–3739.
47. Gandhi, S.J., Minn, AJ., Vonderheide, RH., et al. Awakening the immune system with radiation: Optimal dose and fractionation. Cancer Lett 368:2 (2015), 185–190.
48. Tang, C., Welsh, JW., Groot, P., et al. Ipilimumab with stereotactic ablative radiation therapy: Phase I results and immunologic correlates from peripheral T-cells. Clin Cancer Res, 2016.
49. Hiniker, S.M., Reddy, SA., Maecker, HT., et al. A prospective clinical trial combining radiation therapy with systemic immunotherapy in metastatic melanoma. Int J Radiat Oncol Biol Phys 96:3 (2016), 578–588.
50. Slovin, S.F., 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 24:7 (2013), 1813–1821.
51. Kwon, E.D., 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 15:7 (2014), 700–712.
52. Theurich, S., Rothschild, S.I., Hoffmann, M., et al. Local tumor treatment in combination with systemic ipilimumab immunotherapy prolongs overall survival in patients with advanced malignant melanoma. Cancer Immunol Res, 2016.
53. Mathew, M., Tam, M., Ott, PA., et al. Ipilimumab in melanoma with limited brain metastases treated with stereotactic radiosurgery. Melanoma Res 23:3 (2013), 191–195.
54. Kiess, A.P., 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 92:2 (2015), 368–375.
55. Schoenfeld, J.D., Mahadevan, A, Floyd, SR., et al. Ipilmumab and cranial radiation in metastatic melanoma patients: A case series and review. J Immunother Cancer, 3, 2015, 50.
56. Ahmed, K.A., Stallworth, DG., Kim, Y., et al. Clinical outcomes of melanoma brain metastases treated with stereotactic radiation and anti-PD-1 therapy. Ann Oncol 27:3 (2016), 434–441.
57. Alomari, A.K., Cohen, J., Vortmeyer, AO., et al. Possible interaction of Anti-PD-1 therapy with the effects of radiosurgery on brain metastases. Cancer Immunol Res 4:6 (2016), 481–487.
58. Solmaz, S., Johnstone, PA., Forsyth, PA., et al. Safety and antitumor activity of hypofractionated stereotactic irradiation (HFSRT) with pembrolizumab (Pembro) and bevacizumab (Bev) in patients (pts) with recurrent high grade gliomas: Preliminary results from phase I study. J Clin Oncol, 34(suppl), 2016 [abstract 2041].
59. Segal, N.H., Kemeny, NE., Cercek, A., et al. Non-randomized phase II study to assess the efficacy of pembrolizumab (Pem) plus radiotherapy (RT) or ablation in mismatch repair proficient (pMMR) metastatic colorectal cancer (mCRC) patients. J Clin Oncol, 34(suppl), 2016 [abstract 3539].
60. Durm, G.A., Ebenezer, KA., Fisher, WB., et al. Phase II trial of consolidation pembrolizumab following concurrent chemoradiation in patients (pts) with unresectable or inoperable stage III non-small cell lung cancer (NSCLC): Initial safety data from HCRN LUN 14-179. J Clin Oncol, 34(suppl), 2016 [abstract e20025].
61. Daud, A.I., Loo, K., Pauli, ML., et al. Tumor immune profiling predicts response to anti-PD-1 therapy in human melanoma. J Clin Invest 126:9 (2016), 3447–3452.
62. Vanpouille-Box, C., Diamond, JM., Pliones, KA., et al. TGFbeta Is a master regulator of radiation therapy-induced antitumor immunity. Cancer Res 75:11 (2015), 2232–2242.
63. Kim, J.E., Patel, MA., Mangraviti, A., et al. Combination therapy with anti-PD-1, anti-TIM-3, and focal radiation results in regression of murine gliomas. Clin Cancer Res, 2016.
64. Kroon, P., Gadiot, J., Peeters, M., et al. Concomitant targeting of programmed death-1 (PD-1) and CD137 improves the efficacy of radiotherapy in a mouse model of human BRAFV600-mutant melanoma. Cancer Immunol Immunother 65:6 (2016), 753–763.
65. Larkin, J., Chiarion-Sileni, V., Gonzalez, R., et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 373:1 (2015), 23–34.
66. Johnson, D.B., Balko, JM., Compton, ML., et al. Fulminant myocarditis with combination immune checkpoint blockade. N Engl J Med 375:18 (2016), 1749–1755.
67. Tang, C., Liao, Z., Gomez, D., et al. Lymphopenia association with gross tumor volume and lung V5 and its effects on non-small cell lung cancer patient outcomes. Int J Radiat Oncol Biol Phys 89:5 (2014), 1084–1091.
68. Gameiro, S.R., Malamas, A.S., Bernstein, M.B., et al. Tumor cells surviving exposure to proton or photon radiation share a common immunogenic modulation signature, rendering them more sensitive to T-cell mediated killing. Int J Radiat Oncol Biol Phys 95:1 (2016), 120–130.