Immunotherapy and Radiation Therapy in Renal Cell Carcinoma

Author(s): Veronica Mollica, Matteo Santoni, Vincenzo Di Nunno, Alessia Cimadamore, Liang Cheng, Antonio Lopez-Beltran, Nicola Battelli, Rodolfo Montironi, Francesco Massari*

Journal Name: Current Drug Targets

Volume 21 , Issue 14 , 2020


  Journal Home
Translate in Chinese
Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

Background: The management of renal cell carcinoma is rapidly evolving and immunotherapy, mostly consisting of immune checkpoint inhibitors, is revolutionizing the treatment scenario of metastatic patients. Novel fractionation schedules of radiotherapy, consisting of high doses in few fractions, can overcome the radioresistance of this tumor. Localized radiotherapy is associated with a systemic effect, known as the abscopal effect. This effect mediated by the immune system can be enhanced associating radiotherapy with immunotherapy.

Objective: In this review, we explore the role of radiotherapy and immunotherapy in RCC, the rationale of combining these strategies and the on-going clinical trials investigating combinations of these two treatment modalities.

Conclusion: Combining immunotherapy and radiotherapy has a strong rationale and pre-clinical studies support their association because it can overcome the immunosuppression of the tumor microenvironment and increase the anti-tumor immune response. More clinical evidence, deriving from onclinical trials, are needed to prove the efficacy and safety of these treatments combined.

Keywords: Renal cell carcinoma, radiotherapy, immunotherapy, abscopal effect, immune checkpoint-inhibitors, PD-1/PD-L1 inhibitors.

[1]
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019; 69(1): 7-34.
[http://dx.doi.org/10.3322/caac.21551 ] [PMID: 30620402]
[2]
Moch H, Cubilla AL, Humphrey PA, Reuter VE, Ulbright TM. The 2016 WHO classification of tumours of the urinary system and male genital organs—part A: Renal, penile, and testicular tumours. Eur Urol 2016; 70(1): 93-105.
[http://dx.doi.org/10.1016/j.eururo.2016.02.029 ] [PMID: 26935559]
[3]
Massari F, Di Nunno V, Santoni M, et al. Toward a genome-based treatment landscape for renal cell carcinoma. Crit Rev Oncol Hematol 2019; 142: 141-52.
[http://dx.doi.org/10.1016/j.critrevonc.2019.07.020 ] [PMID: 31401421]
[4]
Ricketts CJ, De Cubas AA, Fan H, et al. Cancer genome atlas research network. the cancer genome atlas comprehensive molecular characterization of renal cell carcinoma. Cell Rep 2018; 23(12): 3698.
[http://dx.doi.org/10.1016/j.celrep.2018.06.032 ] [PMID: 29925010]
[5]
Choueiri TK, Motzer RJ. Systemic therapy for metastatic renal-cell carcinoma. N Engl J Med 2017; 376(4): 354-66.
[http://dx.doi.org/10.1056/NEJMra1601333 ] [PMID: 28121507]
[6]
Mollica V, Di Nunno V, Gatto L, et al. Novel therapeutic approaches and targets currently under evaluation for renal cell carcinoma: waiting for the revolution. Clin Drug Investig 2019; 39(6): 503-19.
[http://dx.doi.org/10.1007/s40261-019-00773-w ] [PMID: 30937824]
[7]
Dengina N, Tsimafeyeu I, Mitin T. Current role of radiotherapy for renal-cell carcinoma. [review]. Clin Genitourin Cancer 2017; 15(2): 183-7.
[http://dx.doi.org/10.1016/j.clgc.2016.09.004 ] [PMID: 27789182]
[8]
Motzer RJ, Escudier B, McDermott DF, et al. CheckMate 025 Investigators. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med 2015; 373(19): 1803-13.
[http://dx.doi.org/10.1056/NEJMoa1510665 ] [PMID: 26406148]
[9]
Motzer RJ, Tannir NM, McDermott DF, et al. CheckMate 214 Investigators. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med 2018; 378(14): 1277-90.
[http://dx.doi.org/10.1056/NEJMoa1712126 ] [PMID: 29562145]
[10]
Motzer RJ, Rini BI, McDermott DF, et al. CheckMate 214 investigators. Nivolumab plus ipilimumab versus sunitinib in first-line treatment for advanced renal cell carcinoma: extended follow-up of efficacy and safety results from a randomised, controlled, phase 3 trial. Lancet Oncol 2019; 20(10): 1370-85.
[http://dx.doi.org/10.1016/S1470-2045(19)30413-9 ] [PMID: 31427204]
[11]
Rini BI, Plimack ER, Stus V, et al. KEYNOTE-426 Investigators. pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med 2019; 380(12): 1116-27.
[http://dx.doi.org/10.1056/NEJMoa1816714 ] [PMID: 30779529]
[12]
Motzer RJ, Penkov K, Haanen J, et al. Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med 2019; 380(12): 1103-15.
[http://dx.doi.org/10.1056/NEJMoa1816047 ] [PMID: 30779531]
[13]
McKay RR, McGregor BA, Gray K, et al. Results of a phase II study of atezolizumab and bevacizumab in non-clear cell renal cell carcinoma (nccRCC) and clear cell renal cell carcinoma with sarcomatoid differentiation (sccRCC). J Clin Oncol 2019; 37(no7_suppl): 548-8.
[14]
Flippot R, McGregor BA, Flaidel A, et al. Atezolizumab plus bevacizumab in non-clear cell renal cell carcinoma (NccRCC) and clear cell renal cell carcinoma with sarcomatoid differentiation (ccRCCsd): Updated results of activity and predictive biomarkers from a phase II study. J Clin Oncol 2019; 37(no15_suppl): 4583-3.
[15]
McDermott DF, Lee J-L, Ziobro M, et al. First-line pembrolizumab (pembro) monotherapy for advanced non-clear cell renal cell carcinoma (nccRCC): Results from KEYNOTE-427 cohort B. J Clin Oncol 2019; 37(no7_suppl): 546-6.
[16]
Chen DS, Mellman I. Elements of cancer immunity and the cancer-immune set point. Nature 2017; 541(7637): 321-30.
[http://dx.doi.org/10.1038/nature21349 ] [PMID: 28102259]
[17]
Alexandrov LB, Nik-Zainal S, Wedge DC, et al. Australian Pancreatic Cancer Genome Initiative; ICGC Breast Cancer Consortium; ICGC MMML-Seq Consortium; ICGC PedBrain. Signatures of mutational processes in human cancer. Nature 2013; 500(7463): 415-21.
[http://dx.doi.org/10.1038/nature12477 ] [PMID: 23945592]
[18]
Samstein RM, Lee CH, Shoushtari AN, et al. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet 2019; 51(2): 202-6.
[http://dx.doi.org/10.1038/s41588-018-0312-8 ] [PMID: 30643254]
[19]
McDermott DF, Huseni MA, Atkins MB, et al. Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma. Nat Med 2018; 24(6): 749-57.
[http://dx.doi.org/10.1038/s41591-018-0053-3 ] [PMID: 29867230]
[20]
De Meerleer G, Khoo V, Escudier B, et al. Radiotherapy for renal-cell carcinoma. Lancet Oncol 2014; 15(4): e170-7.
[http://dx.doi.org/10.1016/S1470-2045(13)70569-2 ] [PMID: 24694640]
[21]
Escudier B, Porta C, Schmidinger M, et al. ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2019; 30(5): 706-20.
[http://dx.doi.org/10.1093/annonc/mdz056 ] [PMID: 30788497/]
[22]
Haimovitz-Friedman A, Kan CC, Ehleiter D, et al. Ionizing radiation acts on cellular membranes to generate ceramide and initiate apoptosis. J Exp Med 1994; 180(2): 525-35.
[http://dx.doi.org/10.1084/jem.180.2.525 ] [PMID: 8046331]
[23]
Stinauer MA, Kavanagh BD, Schefter TE, et al. Stereotactic body radiation therapy for melanoma and renal cell carcinoma: impact of single fraction equivalent dose on local control. Radiat Oncol 2011; 6: 34.
[http://dx.doi.org/10.1186/1748-717X-6-34 ] [PMID: 21477295]
[24]
Garcia-Barros M, Paris F, Cordon-Cardo C, et al. Tumor response to radiotherapy regulated by endothelial cell apoptosis. Science 2003; 300(5622): 1155-9.
[http://dx.doi.org/10.1126/science.1082504 ] [PMID: 12750523]
[25]
Gulbins E. Regulation of death receptor signaling and apoptosis by ceramide. Pharmacol Res 2003; 47(5): 393-9.
[http://dx.doi.org/10.1016/S1043-6618(03)00052-5 ] [PMID: 12676513]
[26]
Li J, Yu W, Tiwary R, et al. α-TEA-induced death receptor dependent apoptosis involves activation of acid sphingomyelinase and elevated ceramide-enriched cell surface membranes. Cancer Cell Int 2010; 10: 40.
[http://dx.doi.org/10.1186/1475-2867-10-40 ] [PMID: 12676513]
[27]
Kolesnick R, Fuks Z. Radiation and ceramide-induced apoptosis. Oncogene 2003; 22(37): 5897-906.
[http://dx.doi.org/10.1038/sj.onc.1206702 ] [PMID: 20974006]
[28]
Fuks Z, Kolesnick R. Engaging the vascular component of the tumor response. Cancer Cell 2005; 8(2): 89-91.
[http://dx.doi.org/10.1016/j.ccr.2005.07.014 ] [PMID: 12947396]
[29]
Kjaer M, Frederiksen PL, Engelholm SA. Postoperative radiotherapy in stage II and III renal adenocarcinoma. A randomized trial by the Copenhagen Renal Cancer Study Group. Int J Radiat Oncol Biol Phys 1987; 13(5): 665-72.
[http://dx.doi.org/10.1016/0360-3016(87)90283-5 ] [PMID: 3553111]
[30]
Wersäll PJ, Blomgren H, Lax I, et al. Extracranial stereotactic radiotherapy for primary and metastatic renal cell carcinoma. Radiother Oncol 2005; 77(1): 88-95.
[http://dx.doi.org/10.1016/j.radonc.2005.03.022 ] [PMID: 15972239]
[31]
Beitler JJ, Makara D, Silverman P, Lederman G. Definitive, high-dose-per-fraction, conformal, stereotactic external radiation for renal cell carcinoma. Am J Clin Oncol 2004; 27(6): 646-8.
[http://dx.doi.org/10.1097/01.coc.0000145289.57705.07 ] [PMID: 15577450]
[32]
Svedman C, Karlsson K, Rutkowska E, et al. Stereotactic body radiotherapy of primary and metastatic renal lesions for patients with only one functioning kidney. Acta Oncol 2008; 47(8): 1578-83.
[http://dx.doi.org/10.1080/02841860802123196 ] [PMID: 18607859]
[33]
Nomiya T, Tsuji H, Hirasawa N, et al. Carbon ion radiation therapy for primary renal cell carcinoma: initial clinical experience. Int J Radiat Oncol Biol Phys 2008; 72(3): 828-33.
[http://dx.doi.org/10.1016/j.ijrobp.2008.01.043 ] [PMID: 18374507]
[34]
Siva S, Pham D, Gill S, Corcoran NM, Foroudi F. A systematic review of stereotactic radiotherapy ablation for primary renal cell carcinoma. BJU Int 2012; 110(11 Pt B): E737-43.
[http://dx.doi.org/10.1111/j.1464-410X.2012.11550.x ] [PMID: 23107102]
[35]
Siva S, Louie AV, Warner A, et al. Pooled analysis of stereotactic ablative radiotherapy for primary renal cell carcinoma: A report from the International Radiosurgery Oncology Consortium for Kidney (IROCK). Cancer 2018; 124(5): 934-42.
[http://dx.doi.org/10.1002/cncr.31156 ] [PMID: 29266183]
[36]
Fokas E, Henzel M, Hamm K, Surber G, Kleinert G, Engenhart-Cabillic R. Radiotherapy for brain metastases from renal cell cancer: should whole-brain radiotherapy be added to stereotactic radiosurgery?: analysis of 88 patients. Strahlenther Onkol 2010; 186(4): 210-7.
[http://dx.doi.org/10.1007/s00066-010-2055-z ] [PMID: 20165820]
[37]
Ikushima H, Tokuuye K, Sumi M, et al. Fractionated stereotactic radiotherapy of brain metastases from renal cell carcinoma. Int J Radiat Oncol Biol Phys 2000; 48(5): 1389-93.
[http://dx.doi.org/10.1016/S0360-3016(00)00804-X ] [PMID: 11121638]
[38]
Andrews DW, Scott CB, Sperduto PW, et al. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet 2004; 363(9422): 1665-72.
[http://dx.doi.org/10.1016/S0140-6736(04)16250-8 ] [PMID: 15158627]
[39]
Kocher M, Soffietti R, Abacioglu U, et al. Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study. J Clin Oncol 2011; 29(2): 134-41.
[http://dx.doi.org/10.1200/JCO.2010.30.1655 ] [PMID: 21041710]
[40]
Prabhu RS, Patel KR, Press RH, et al. Preoperative vs postoperative radio- surgery for resected brain metastases: a review. Neurosurgery 2019; 84(1): 19-29.
[http://dx.doi.org/10.1093/neuros/nyy146 ] [PMID: 29771381]
[41]
NCCN Clinical Practice Guidelines in Oncology. Kidney Cancer. Version 2 2019 August;
[42]
Zelefsky MJ, Greco C, Motzer R, et al. Tumor control outcomes after hypofractionated and single-dose stereotactic image-guided intensity-modulated radiotherapy for extracranial metastases from renal cell carcinoma. Int J Radiat Oncol Biol Phys 2012; 82(5): 1744-8.
[http://dx.doi.org/10.1016/j.ijrobp.2011.02.040 ] [PMID: 21596489]
[43]
Hunter GK, Balagamwala EH, Koyfman SA, et al. The efficacy of external beam radiotherapy and stereotactic body radiotherapy for painful spinal metastases from renal cell carcinoma. Pract Radiat Oncol 2012; 2(4): e95-e100.
[http://dx.doi.org/10.1016/j.prro.2012.01.005 ] [PMID: 24674192]
[44]
Siva S, MacManus MP, Martin RF, Martin OA. Abscopal effects of radiation therapy: a clinical review for the radiobiologist. Cancer Lett 2015; 356(1): 82-90.
[http://dx.doi.org/10.1016/j.canlet.2013.09.018 ] [PMID: 24125863]
[45]
Formenti SC, Demaria S. Systemic effects of local radiotherapy. Lancet Oncol 2009; 10(7): 718-26.
[http://dx.doi.org/10.1016/S1470-2045(09)70082-8 ] [PMID: 19573801]
[46]
Mole RH. Whole body irradiation; radiobiology or medicine? Br J Radiol 1953; 26(305): 234-41.
[http://dx.doi.org/10.1259/0007-1285-26-305-234 ] [PMID: 13042090]
[47]
Abuodeh Y, Venkat P, Kim S. Systematic review of case reports on the abscopal effect Curr Probl Cancer 2016; b40(1): b25-371474 Current Drug Targets, 2020, Vol 21, No 14 Mollica et al
[http://dx.doi.org/10.1016/j.currproblcancer.2015.10.001]
[48]
Wersäll PJ, Blomgren H, Pisa P, Lax I, Kälkner KM, Svedman C. Regression of non-irradiated metastases after extracranial stereotactic radiotherapy in metastatic renal cell carcinoma. Acta Oncol 2006; 45(4): 493-7.
[http://dx.doi.org/10.1080/02841860600604611 ] [PMID: 16760190]
[49]
Hu ZI, McArthur HL, Ho AY. The abscopal effect of radiation therapy: what is it and how can we use it in breast cancer? Curr Breast Cancer Rep 2017; 9(1): 45-51.
[http://dx.doi.org/10.1007/s12609-017-0234-y ] [PMID: 28344743]
[50]
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): 925-31.
[http://dx.doi.org/10.1056/NEJMoa1112824 ] [PMID: 22397654]
[51]
Ohba K, Omagari K, Nakamura T, et al. Abscopal regression of hepatocellular carcinoma after radiotherapy for bone metastasis. Gut 1998; 43(4): 575-7.
[http://dx.doi.org/10.1136/gut.43.4.575 ] [PMID: 9824589]
[52]
Grass GD, Krishna N, Kim S. The immune mechanisms of abscopal effect in radiation therapy. Curr Probl Cancer 2016; 40(1): 10-24.
[http://dx.doi.org/10.1016/j.currproblcancer.2015.10.003 ] [PMID: 26612692]
[53]
Gupta A, Probst HC, Vuong V, et al. Radiotherapy promotes tumor-specific effector CD8+ T cells via dendritic cell activation. J Immunol 2012; 189(2): 558-66.
[http://dx.doi.org/10.4049/jimmunol.1200563 ] [PMID: 22685313]
[54]
Liu Y, Dong Y, Kong L, Shi F, Zhu H, Yu J. Abscopal effect of radiotherapy combined with immune checkpoint inhibitors. J Hematol Oncol 2018; 11(1): 104.
[http://dx.doi.org/10.1186/s13045-018-0647-8 ] [PMID: 30115069]
[55]
Barker HE, Paget JT, Khan AA, Harrington KJ. The tumour microenvironment after radiotherapy: mechanisms of resistance and recurrence. Nat Rev Cancer 2015; 15(7): 409-25.
[http://dx.doi.org/10.1038/nrc3958 ] [PMID: 26105538]
[56]
Langley RE, Bump EA, Quartuccio SG, Medeiros D, Braunhut SJ. Radiation-induced apoptosis in microvascular endothelial cells. Br J Cancer 1997; 75(5): 666-72.
[http://dx.doi.org/10.1038/bjc.1997.119 ] [PMID: 9043022]
[57]
Schaue D, McBride WH. Links between innate immunity and normal tissue radiobiology. Radiat Res 2010; 173(4): 406-17.
[http://dx.doi.org/10.1667/RR1931.1 ] [PMID: 20334512]
[58]
Ozsoy HZ, Sivasubramanian N, Wieder ED, Pedersen S, Mann DL. Oxidative stress promotes ligand-independent and enhanced ligand-dependent tumor necrosis factor receptor signaling. J Biol Chem 2008; 283(34): 23419-28.
[http://dx.doi.org/10.1074/jbc.M802967200 ] [PMID: 18544535]
[59]
Krysko DV, Garg AD, Kaczmarek A, Krysko O, Agostinis P, Vandenabeele P. Immunogenic cell death and DAMPs in cancer therapy. Nat Rev Cancer 2012; 12(12): 860-75.
[http://dx.doi.org/10.1038/nrc3380 ] [PMID: 23151605]
[60]
Apetoh L, Ghiringhelli F, Tesniere A, et al. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med 2007; 13(9): 1050-9.
[http://dx.doi.org/10.1038/nm1622 ] [PMID: 17704786]
[61]
Vatner RE, Cooper BT, Vanpouille-Box C, Demaria S, Formenti SC. Combinations of immunotherapy and radiation in cancer therapy. Front Oncol 2014; 4: 325.
[http://dx.doi.org/10.3389/fonc.2014.00325 ] [PMID: 25506582]
[62]
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(7): 2488-96.
[http://dx.doi.org/10.1158/0008-5472.CAN-10-2820 ] [PMID: 21300764]
[63]
Fuertes MB, Kacha AK, Kline J, et al. Host type I IFN signals are required for antitumor CD8+ T cell responses through CD8alpha+ dendritic cells. J Exp Med 2011; 208(10): 2005-16.
[http://dx.doi.org/10.1084/jem.20101159 ] [PMID: 21930765]
[64]
Lugade AA, Sorensen EW, Gerber SA, Moran JP, Frelinger JG, Lord EM. Radiation-induced IFN-gamma production within the tumor microenvironment influences antitumor immunity. J Immunol 2008; 180(5): 3132-9.
[http://dx.doi.org/10.4049/jimmunol.180.5.3132 ] [PMID: 18292536]
[65]
Vanpouille-Box C, Diamond JM, Pilones KA, et al. TGFbeta is a master regulator of radiation therapy-induced antitumor immunity. Cancer Res 2015; 75(11): 2232-42.
[http://dx.doi.org/10.1158/0008-5472.CAN-14-3511 ] [PMID: 25858148]
[66]
Wrzesinski SH, Wan YY, Flavell RA. Transforming growth factor-beta and the immune response: implications for anticancer therapy. Clin Cancer Res 2007; 13(18 Pt 1): 5262-70.
[http://dx.doi.org/10.1158/1078-0432.CCR-07-1157 ] [PMID: 17875754]
[67]
Bouquet F, Pal A, Pilones KA, et al. TGFβ1 inhibition increases the radiosensitivity of breast cancer cells in vitro and promotes tumor control by radiation in vivo. Clin Cancer Res 2011; 17(21): 6754-65.
[http://dx.doi.org/10.1158/1078-0432.CCR-11-0544 ] [PMID: 22028490]
[68]
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): 7516-23.
[http://dx.doi.org/10.4049/jimmunol.174.12.7516 ] [PMID: 15944250]
[69]
Kachikwu EL, Iwamoto KS, Liao YP, et al. Radiation enhances regulatory T cell representation. Int J Radiat Oncol Biol Phys 2011; 81(4): 1128-35.
[http://dx.doi.org/10.1016/j.ijrobp.2010.09.034 ] [PMID: 21093169]
[70]
Laoui D, Van Overmeire E, De Baetselier P, Van Ginderachter JA, Raes G. Functional relationship between tumor-associated macrophages and macrophage colony-stimulating factor as contributors to cancer progression. Front Immunol 2014; 5: 489.
[http://dx.doi.org/10.3389/fimmu.2014.00489 ] [PMID: 25339957]
[71]
Demaria S, Ng B, Devitt ML, 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.
[http://dx.doi.org/10.1016/j.ijrobp.2003.09.012 ] [PMID: 14967443]
[72]
Chakravarty PK, Alfieri A, Thomas EK, et al. Flt3-ligand administration after radiation therapy prolongs survival in a murine model of metastatic lung cancer. Cancer Res 1999; 59(24): 6028-32.
[PMID: 10626784]
[73]
Camphausen K, Moses MA, Ménard C, et al. Radiation abscopal antitumor effect is mediated through p53. Cancer Res 2003; 63(8): 1990-3.
[PMID: 12702593]
[74]
Ngwa W, Irabor OC, Schoenfeld JD, Hesser J, Demaria S, Formenti SC. Using immunotherapy to boost the abscopal effect. Nat Rev Cancer 2018; 18(5): 313-22.
[http://dx.doi.org/10.1038/nrc.2018.6 ] [PMID: 29449659]
[75]
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(3): 589-95.
[http://dx.doi.org/10.1182/blood-2009-02-206870 ] [PMID: 19349616]
[76]
Salama AK, Postow MA, Salama JK. Irradiation and immunotherapy: From concept to the clinic. Cancer 2016; 122(11): 1659-71.
[http://dx.doi.org/10.1002/cncr.29889 ] [PMID: 26914620]
[77]
Shahabi V, Postow MA, Tuck D, Wolchok JD. Immune-priming of the tumor microenvironment by radiotherapy: rationale for combination with immunotherapy to improve anticancer efficacy. Am J Clin Oncol 2015; 38(1): 90-7.
[http://dx.doi.org/10.1097/COC.0b013e3182868ec8 ] [PMID: 25616204]
[78]
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.
[PMID: 15701862]
[79]
Akutsu Y, Matsubara H, Urashima T, et al. Combination of direct intratumoral administration of dendritic cells and irradiation induces strong systemic antitumor effect mediated by GRP94/gp96 against squamous cell carcinoma in mice. Int J Oncol 2007; 31(3): 509-15.
[http://dx.doi.org/10.3892/ijo.31.3.509 ] [PMID: 17671676]
[80]
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(17): 5379-88.
[http://dx.doi.org/10.1158/1078-0432.CCR-09-0265 ] [PMID: 19706802]
[81]
Nikitina EY, Gabrilovich DI. Combination of gamma-irradiation and dendritic cell administration induces a potent antitumor response in tumor-bearing mice: approach to treatment of advanced stage cancer. Int J Cancer 2001; 94(6): 825-33.
[http://dx.doi.org/10.1002/1097-0215(20011215)94:6<825::AID-IJC1545>3.0.CO;2-5 ] [PMID: 11745485]
[82]
Kim KW, Kim SH, Shin JG, et al. Direct injection of immature dendritic cells into irradiated tumor induces efficient antitumor immunity. Int J Cancer 2004; 109(5): 685-90.
[http://dx.doi.org/10.1002/ijc.20036 ] [PMID: 14999775]
[83]
Marconi R, Strolin S, Bossi G, Strigari L. A meta-analysis of the abscopal effect in preclinical models: Is the biologically effective dose a relevant physical trigger? PLoS One 2017; 12(2)e0171559
[http://dx.doi.org/10.1371/journal.pone.0171559 ] [PMID: 28222111]
[84]
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 2015; 21(16): 3727-39.
[http://dx.doi.org/10.1158/1078-0432.CCR-14-2824 ] [PMID: 25869387]
[85]
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): 5458-68.
[http://dx.doi.org/10.1158/0008-5472.CAN-14-1258 ] [PMID: 25274032]
[86]
Parmentier C, Morardet N, Tubiana M. Late effects on human bone marrow after extended field radiotherapy. Int J Radiat Oncol Biol Phys 1983; 9(9): 1303-11.
[http://dx.doi.org/10.1016/0360-3016(83)90261-4 ] [PMID: 6885543]
[87]
Finkelstein SE, Timmerman R, McBride WH, et al. The confluence of stereotactic ablative radiotherapy and tumor immunology. Clin Dev Immunol 2011.2011439752
[http://dx.doi.org/10.1155/2011/439752 ] [PMID: 22162711]
[88]
Young KH, Baird JR, Savage T, et al. Optimizing timing of immunotherapy improves control of tumors by hypofractionated radiation therapy. PLoS One 2016; 11(6)e0157164
[http://dx.doi.org/10.1371/journal.pone.0157164 ] [PMID: 27281029]
[89]
Kang J, Demaria S, Formenti S. Current clinical trials testing the combination of immunotherapy with radiotherapy. J Immunother Cancer 2016; 4: 51.
[http://dx.doi.org/10.1186/s40425-016-0156-7 ] [PMID: 27660705]
[90]
McNamee EN, Korns Johnson D, Homann D, Clambey ET. Hypoxia and hypoxia-inducible factors as regulators of T cell development, differentiation, and function. Immunol Res 2013; 55(1-3): 58-70.
[http://dx.doi.org/10.1007/s12026-012-8349-8 ] [PMID: 22961658]
[91]
Doedens AL, Stockmann C, Rubinstein MP, et al. Macrophage expression of hypoxia-inducible factor-1 alpha suppresses T-cell function and promotes tumor progression. Cancer Res 2010; 70(19): 7465-75.
[http://dx.doi.org/10.1158/0008-5472.CAN-10-1439 ] [PMID: 20841473]
[92]
Qureshi OS, Zheng Y, Nakamura K, et al. Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4. Science 2011; 332(6029): 600-3.
[http://dx.doi.org/10.1126/science.1202947 ] [PMID: 21474713]
[93]
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.
[http://dx.doi.org/10.1016/S1470-2045(15)00007-8 ] [PMID: 26433823]
[94]
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(4): 345-55.
[http://dx.doi.org/10.1158/2326-6066.CIR-14-0196 ] [PMID: 25527358]
[95]
Park SS, Dong H, Liu X, et al. PD-1 restrains radiotherapy-induced abscopal effect. Cancer Immunol Res 2015; 3(6): 610-9.
[http://dx.doi.org/10.1158/2326-6066.CIR-14-0138 ] [PMID: 25701325]
[96]
Buttigliero C, Allis S, Tucci M, et al. Role of radiotherapy in improving activity of immune-modulating drugs in advanced renal cancer: Biological rationale and clinical evidences. Cancer Treat Rev 2018; 69: 215-23.
[http://dx.doi.org/10.1016/j.ctrv.2018.07.010 ] [PMID: 30096699]
[97]
Grosso JF, Jure-Kunkel MN. CTLA-4 blockade in tumor models: an overview of preclinical and translational research. Cancer Immun 2013; 13: 5.
[PMID: 23390376]
[98]
Salama AK, Hodi FS. Cytotoxic T-lymphocyte-associated antigen-4. Clin Cancer Res 2011; 17(14): 4622-8.
[http://dx.doi.org/10.1158/1078-0432.CCR-10-2232 ] [PMID: 21467163]
[99]
Pedicord VA, Montalvo W, Leiner IM, Allison JP. Single dose of anti-CTLA-4 enhances CD8+ T-cell memory formation, function, and maintenance. Proc Natl Acad Sci USA 2011; 108(1): 266-71.
[http://dx.doi.org/10.1073/pnas.1016791108 ] [PMID: 21173239]
[100]
Grimaldi AM, Simeone E, Giannarelli D, et al. Abscopal effects of radiotherapy on advanced melanoma patients who progressed after ipilimumab immunotherapyOncoImmunology 2014; 3e28780
[http://dx.doi.org/10.4161/onci.28780 ] [PMID: 25083318]
[101]
Koller KM, Mackley HB, Liu J, et al. Improved survival and complete response rates in patients with advanced melanoma treated with concurrent ipilimumab and radiotherapy versus ipilimumab alone. Cancer Biol Ther 2017; 18(1): 36-42.
[http://dx.doi.org/10.1080/15384047.2016.1264543 ] [PMID: 27905824]
[102]
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(2): 687-95.
[http://dx.doi.org/10.1172/JCI67313 ] [PMID: 24382348]
[103]
Teng F, Kong L, Meng X, Yang J, Yu J. Radiotherapy combined with immune checkpoint blockade immunotherapy: Achievements and challenges. Cancer Lett 2015; 365(1): 23-9.
[http://dx.doi.org/10.1016/j.canlet.2015.05.012 ] [PMID: 25980820]
[104]
Haanen JBAG, Carbonnel F, Robert C, et al. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2017; 29(Supplement_4): iv264-6..
[105]
Zaorsky NG, Lehrer EJ, Kothari G, Louie AV, Siva S. Stereotactic ablative radiation therapy for oligometastatic renal cell carcinoma (SABR ORCA): a meta-analysis of 28 studies. Eur Urol Oncol 2019; 2(5): 515-23.
[http://dx.doi.org/10.1016/j.euo.2019.05.007 ] [PMID: 31302061]
[106]
Pierce RH, Campbell JS, Pai SI, et al. In-situ tumor vaccination: bringing the fight to the tumor. Hum Vaccin Immunother 2015; 11: 1901-9.
[http://dx.doi.org/10.1080/21645515.2015.1049779]
[107]
Kohrt HE, Chu J, Brody J, et al. Dose-escalated, intratumoral TLR9 agonist and low-dose radiation induce abscopal effects in follicular lymphoma. Blood 2014; 124: 3092.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 21
ISSUE: 14
Year: 2020
Published on: 20 October, 2020
Page: [1463 - 1475]
Pages: 13
DOI: 10.2174/1389450121666200311121540
Price: $65

Article Metrics

PDF: 26
HTML: 1