Digestive Disease Interventions 2020; 04(04): 382-388
DOI: 10.1055/s-0040-1721454
Review Article

Combination Therapies with Y90: Immunoradiation

1   Interventional Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York
,
2   Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
,
Joseph P. Erinjeri
1   Interventional Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York
,
Yolanda C.D. Bryce
1   Interventional Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York
› Author Affiliations
Funding This research was partly funded through the NIH/NCI Cancer Center Support Grant P30 CA008748. A.R.D. reports personal fees from BTG, Inc, personal fees from Dova Pharmaceuticals, outside the submitted work. J.P.E. reports personal fees from AstraZeneca and Canon, United States, Inc.

Abstract

While much progress has been made in oncologic care, metastatic solid organ cancer still carries a poor prognosis. Immunotherapy has emerged as a promising approach, though in most patients, does not control disease when given as a monotherapy. Combining immunotherapy with locoregional therapy is one approach to boost the efficacy of treatments and potentially prolong survival. Most of the researches regarding combination therapies have involved external radiation. This review describes the immunologic effects of external radiation and radioembolization, and how these effects provide a rationale for combining hepatic radioembolization with immunotherapy.



Publication History

Received: 09 July 2020

Accepted: 06 October 2020

Article published online:
19 November 2020

© 2020. Thieme. All rights reserved.

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  • References

  • 1 Howlader N, Noone A, Krapcho M. et al. SEER Cancer Statistics Review, 1975–2014. Bethesda, MD: National Cancer Institute; 2017: 1-12
  • 2 DeSantis CE, Ma J, Gaudet MM. et al. Breast cancer statistics, 2019. CA Cancer J Clin 2019; 69 (06) 438-451
  • 3 Mansoori B, Mohammadi A, Davudian S, Shirjang S, Baradaran B. The different mechanisms of cancer drug resistance: a brief review. Adv Pharm Bull 2017; 7 (03) 339-348
  • 4 Couzin-Frankel J. Breakthrough of the year 2013. Cancer immunotherapy. Science 2013; 342 (6165): 1432-1433
  • 5 Wang RF. A special issue on cancer immunotherapy. Cell Res 2017; 27 (01) 1-2
  • 6 Kaminski JM, Shinohara E, Summers JB, Niermann KJ, Morimoto A, Brousal J. The controversial abscopal effect. Cancer Treat Rev 2005; 31 (03) 159-172
  • 7 Erinjeri JP, Sze DT. Immunotherapy and checkpoint inhibitors: a primer for the interventional radiologist. Endovascular Today 2019. Available at: https://evtoday.com/articles/2019-oct/immunotherapy-and-checkpoint-inhibitors-a-primer-for-the-interventional-radiologist. Accessed November 1, 2020
  • 8 Hargadon KM, Johnson CE, Williams CJ. Immune checkpoint blockade therapy for cancer: an overview of FDA-approved immune checkpoint inhibitors. Int Immunopharmacol 2018; 62: 29-39
  • 9 Schumacher TN, Schreiber RD. Neoantigens in cancer immunotherapy. Science 2015; 348 (6230): 69-74
  • 10 Hodi FS, O'Day SJ, McDermott DF. et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010; 363 (08) 711-723
  • 11 Pusztai L, Karn T, Safonov A, Abu-Khalaf MM, Bianchini G. New strategies in breast cancer: immunotherapy. Clin Cancer Res 2016; 22 (09) 2105-2110
  • 12 Erinjeri JP, Fine GC, Adema GJ. et al. Immunotherapy and the interventional oncologist: challenges and opportunities—a society of interventional oncology white paper. Radiology 2019; 292 (01) 25-34
  • 13 Chandra RA, Wilhite TJ, Balboni TA. et al. A systematic evaluation of abscopal responses following radiotherapy in patients with metastatic melanoma treated with ipilimumab. OncoImmunology 2015; 4 (11) e1046028
  • 14 Demaria S, Golden EB, Formenti SC. Role of local radiation therapy in cancer immunotherapy. JAMA Oncol 2015; 1 (09) 1325-1332
  • 15 Derer A, Frey B, Fietkau R, Gaipl US. Immune-modulating properties of ionizing radiation: rationale for the treatment of cancer by combination radiotherapy and immune checkpoint inhibitors. Cancer Immunol Immunother 2016; 65 (07) 779-786
  • 16 Reynders K, Illidge T, Siva S, Chang JY, De Ruysscher D. The abscopal effect of local radiotherapy: using immunotherapy to make a rare event clinically relevant. Cancer Treat Rev 2015; 41 (06) 503-510
  • 17 Wattenberg MM, Fahim A, Ahmed MM, Hodge JW. Unlocking the combination: potentiation of radiation-induced antitumor responses with immunotherapy. Radiat Res 2014; 182 (02) 126-138
  • 18 Patel RB, Baniel CC, Sriramaneni RN, Bradley K, Markovina S, Morris ZS. Combining brachytherapy and immunotherapy to achieve in situ tumor vaccination: a review of cooperative mechanisms and clinical opportunities. Brachytherapy 2018; 17 (06) 995-1003
  • 19 Kirkpatrick JP, Kelsey CR, Palta M. et al. Stereotactic body radiotherapy: a critical review for nonradiation oncologists. Cancer 2014; 120 (07) 942-954
  • 20 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 (05) 1229-1235
  • 21 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 (12) 7516-7523
  • 22 Slaney CY, Kershaw MH, Darcy PK. Trafficking of T cells into tumors. Cancer Res 2014; 74 (24) 7168-7174
  • 23 Matsumura S, Wang B, Kawashima N. et al. Radiation-induced CXCL16 release by breast cancer cells attracts effector T cells. J Immunol 2008; 181 (05) 3099-3107
  • 24 Laufer JM, Legler DF. Beyond migration-chemokines in lymphocyte priming, differentiation, and modulating effector functions. J Leukoc Biol 2018; 104 (02) 301-312
  • 25 Huang AY, Golumbek P, Ahmadzadeh M, Jaffee E, Pardoll D, Levitsky H. Role of bone marrow-derived cells in presenting MHC class I-restricted tumor antigens. Science 1994; 264 (5161): 961-965
  • 26 Fonteneau J-F, Larsson M, Bhardwaj N. Interactions between dead cells and dendritic cells in the induction of antiviral CTL responses. Curr Opin Immunol 2002; 14 (04) 471-477
  • 27 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 (03) 589-595
  • 28 Burnette BC, Liang H, Lee Y. et al. The efficacy of radiotherapy relies upon induction of type i interferon-dependent innate and adaptive immunity. Cancer Res 2011; 71 (07) 2488-2496
  • 29 Deng L, Liang H, Xu M. et al. STING-dependent cytosolic DNA sensing promotes radiation-induced type I interferon-dependent antitumor immunity in immunogenic tumors. Immunity 2014; 41 (05) 843-852
  • 30 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
  • 31 Golden EB, Apetoh L. Radiotherapy and immunogenic cell death. Semin Radiat Oncol 2015; 25 (01) 11-17
  • 32 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 (05) 1259-1271
  • 33 Vanpouille-Box C, Alard A, Aryankalayil MJ. et al. DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity. Nat Commun 2017; 8: 15618
  • 34 Nesslinger NJ, Sahota RA, Stone B. et al. Standard treatments induce antigen-specific immune responses in prostate cancer. Clin Cancer Res 2007; 13 (05) 1493-1502
  • 35 Formenti SC, Demaria S. Radiation therapy to convert the tumor into an in situ vaccine. Int J Radiat Oncol Biol Phys 2012; 84: 879-880
  • 36 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 (02) 687-695
  • 37 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 (19) 5458-5468
  • 38 Gupta A, Probst HC, Vuong V. et al. Radiotherapy promotes tumor-specific effector CD8+ T cells via dendritic cell activation. J Immunol 2012; 189 (02) 558-566
  • 39 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 (10) 925-931
  • 40 Crittenden M, Kohrt H, Levy R. et al. Current clinical trials testing combinations of immunotherapy and radiation. Semin Radiat Oncol 2015; 25 (01) 54-64
  • 41 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 (05) 986-997
  • 42 Luke JJ, Lemons JM, Karrison TG. et al. Safety and clinical activity of pembrolizumab and multisite stereotactic body radiotherapy in patients with advanced solid tumors. J Clin Oncol 2018; 36 (16) 1611-1618
  • 43 Shaverdian N, Lisberg AE, Bornazyan K. et al. Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: a secondary analysis of the KEYNOTE-001 phase 1 trial. Lancet Oncol 2017; 18 (07) 895-903
  • 44 Robin TP, Breeze RE, Smith DE. et al. Immune checkpoint inhibitors and radiosurgery for newly diagnosed melanoma brain metastases. J Neurooncol 2018; 140 (01) 55-62
  • 45 Tang C, Welsh JW, de Groot P. et al. Ipilimumab with stereotactic ablative radiation therapy: phase I results and immunologic correlates from peripheral T-cells. Clin Cancer Res 2017; 23 (06) 1388-1396
  • 46 Demaria S, Formenti SC. Radiation as an immunological adjuvant: current evidence on dose and fractionation. Front Oncol 2012; 2: 153
  • 47 Schaue D, Ratikan JA, Iwamoto KS, McBride WH. Maximizing tumor immunity with fractionated radiation. Int J Radiat Oncol Biol Phys 2012; 83 (04) 1306-1310
  • 48 Pasciak AS, McKinney JM, Bradley YC. Handbook of Radioembolization: Physics, Biology, Nuclear Medicine, and Imaging. Boca Raton: Taylor & Francis; 2017
  • 49 Ghodadra A, Bhatt S, Camacho JC, Kim HS. Abscopal effects and yttrium-90 radioembolization. Cardiovasc Intervent Radiol 2016; 39 (07) 1076-1080
  • 50 Deipolyi AR, Bromberg JF, Erinjeri JP, Solomon SB, Brody LA, Riedl CC. Abscopal effect after radioembolization for metastatic breast cancer in the setting of immunotherapy. J Vasc Interv Radiol 2018; 29 (03) 432-433
  • 51 Powerski M, Drewes R, Omari J, Relja B, Surov A, Pech M. Intra-hepatic abscopal effect following radioembolization of hepatic metastases. Cardiovasc Intervent Radiol 2020; 43 (11) 1641-1649
  • 52 Fernandez-Ros N, Iñarrairaegui M, Paramo JA. et al. Radioembolization of hepatocellular carcinoma activates liver regeneration, induces inflammation and endothelial stress and activates coagulation. Liver Int 2015; 35 (05) 1590-1596
  • 53 Lewandowski RJ, Andreoli JM, Hickey R. et al. Angiogenic response following radioembolization: results from a randomized pilot study of Yttrium-90 with or without sorafenib. J Vasc Interv Radiol 2016; 27 (09) 1329-1336
  • 54 Sukato DC, Tohme S, Chalhoub D. et al. The prognostic role of neutrophil-to-lymphocyte ratio in patients with unresectable hepatocellular carcinoma treated with radioembolization. J Vasc Interv Radiol 2015; 26: 816-824
  • 55 Sacdalan DB, Lucero JA, Sacdalan DL. Prognostic utility of baseline neutrophil-to-lymphocyte ratio in patients receiving immune checkpoint inhibitors: a review and meta-analysis. OncoTargets Ther 2018; 11: 955-965
  • 56 Chew V, Lee YH, Pan L. et al. Immune activation underlies a sustained clinical response to Yttrium-90 radioembolisation in hepatocellular carcinoma. Gut 2019; 68 (02) 335-346
  • 57 Zhan C, Ruohoniemi D, Shanbhogue KP. et al. Safety of combined Yttrium-90 radioembolization and immune checkpoint inhibitor immunotherapy for hepatocellular carcinoma. J Vasc Interv Radiol 2020; 31 (01) 25-34
  • 58 Ruohoniemi DM, Zhan C, Wei J. et al. Safety and effectiveness of Yttrium-90 radioembolization around the time of immune checkpoint inhibitors for unresectable hepatic metastases. J Vasc Interv Radiol 2020; 31 (08) 1233-1241
  • 59 Wang C, Park J, Ouyang C. et al. A pilot feasibility study of Yttrium-90 liver radioembolization followed by durvalumab and tremelimumab in patients with microsatellite stable colorectal cancer liver metastases. Oncologist 2020; 25 (05) 382-e776