Abstract
Radiotherapy is considered a second life in Renal Cell Carcinoma (RCC) patients, mainly due to the introduction of immune checkpoint inhibitors, such as anti-Programmed-death (PD)-1, alone or in combination with anti-Cytotoxic T-Lymphocyte Antigen (CTLA)-4. Several trials are investigating the efficacy/safety of immune checkpoint inhibitors in sequential or combined strategies with radiotherapy. Chimeric Antigen Receptor (CAR)-T cells therapy as a promising approach in cancer patients has opened the way to novel possibilities of integrating therapies. The identification of biomarkers of tumor response to these combinations represents a challenge in RCC, together with the research for the best partner for immunotherapy in metastatic patients. In this review we illustrated preclinical/clinical data on the integration of radiotherapy with immunocheckpoint inhibitors or CART cells in RCC.
Keywords: CAR-T cells, immunocheckpoint inhibitors, immunotherapy, programmed-death-1, radiation therapy, renal cell carcinoma.
Graphical Abstract
[http://dx.doi.org/10.1016/j.ctrv.2014.12.013] [PMID: 25586601]
[http://dx.doi.org/10.1517/14712598.2015.1035251] [PMID: 26063384]
[http://dx.doi.org/10.2174/1389450117666151209115753] [PMID: 26648075]
[http://dx.doi.org/10.1517/17425255.2016.1120287] [PMID: 26565919]
[http://dx.doi.org/10.7573/dic.212528] [PMID: 29899754]
[PMID: 10685660]
[http://dx.doi.org/10.1007/s10456-017-9550-0] [PMID: 28401381]
[http://dx.doi.org/10.1056/NEJMoa1510665] [PMID: 26406148]
[http://dx.doi.org/10.1056/NEJMoa1712126] [PMID: 29562145]
[http://dx.doi.org/10.1016/S1470-2045(18)30081-0] [PMID: 29439857]
[http://dx.doi.org/10.1056/NEJMoa1816714] [PMID: 30779529]
[http://dx.doi.org/10.1016/S1470-2045(18)30107-4] [PMID: 29530667]
[http://dx.doi.org/10.1056/NEJMoa1816047] [PMID: 30779531]
[http://dx.doi.org/10.1016/0360-3016(85)90285-8] [PMID: 2414257]
[http://dx.doi.org/10.21037/jtd.2017.10.108] [PMID: 29268521]
[http://dx.doi.org/10.1155/2015/636918] [PMID: 26681942]
[http://dx.doi.org/10.1038/nrurol.2017.87] [PMID: 28631740]
[http://dx.doi.org/10.1177/1758834017742575] [PMID: 29383033]
[http://dx.doi.org/10.1016/j.molmed.2013.05.007] [PMID: 23831337]
[http://dx.doi.org/10.1126/science.271.5256.1734] [PMID: 8596936]
[http://dx.doi.org/10.1084/jem.20130579] [PMID: 23897981]
[http://dx.doi.org/10.1158/2326-6066.CIR-14-0104] [PMID: 25038199]
[http://dx.doi.org/10.1016/S1470-2045(15)00007-8] [PMID: 26433823]
[http://dx.doi.org/10.1038/nature14292] [PMID: 25754329]
[http://dx.doi.org/10.1158/2326-6066.CIR-17-0134] [PMID: 29180535]
[PMID: 15701862]
[http://dx.doi.org/10.1016/j.ccell.2015.03.015] [PMID: 25873170]
[http://dx.doi.org/10.1038/s41591-018-0232-2] [PMID: 30397353]
[http://dx.doi.org/10.1158/1078-0432.CCR-17-3436] [PMID: 29358500]
[http://dx.doi.org/10.1158/1078-0432.CCR-16-1432] [PMID: 27649551]
[http://dx.doi.org/10.3389/fonc.2014.00325] [PMID: 25506582]
[http://dx.doi.org/10.1002/cncr.25639] [PMID: 20922784]
[http://dx.doi.org/10.2217/imt.15.65] [PMID: 26310908]
[http://dx.doi.org/10.1172/JCI67313] [PMID: 24382348]
[http://dx.doi.org/10.1002/ijc.28503] [PMID: 24114790]
[http://dx.doi.org/10.1034/j.1600-065X.2001.1820102.x] [PMID: 11722621]
[http://dx.doi.org/10.1016/j.intimp.2011.01.030] [PMID: 21315783]
[http://dx.doi.org/10.1158/1078-0432.CCR-17-0802] [PMID: 28679765]
[http://dx.doi.org/10.1016/j.radonc.2017.06.006] [PMID: 28662869]
[http://dx.doi.org/10.1158/2326-6066.CIR-14-0138] [PMID: 25701325]
[http://dx.doi.org/10.1158/2326-6066.CIR-15-0150] [PMID: 26307625]
[http://dx.doi.org/10.1016/j.eururo.2015.07.008] [PMID: 26194044]
[http://dx.doi.org/10.1016/j.eururo.2016.02.049] [PMID: 26947604]
[http://dx.doi.org/10.1634/theoncologist.2018-0205] [PMID: 30104290]
[http://dx.doi.org/10.1073/pnas.86.24.10024] [PMID: 2513569]
[http://dx.doi.org/10.1126/scitranslmed.3002842] [PMID: 21832238]
[http://dx.doi.org/10.1084/jem.20052494] [PMID: 16636135]
[http://dx.doi.org/10.1371/journal.pone.0028217] [PMID: 22140550]
[http://dx.doi.org/10.1006/clim.2000.4945] [PMID: 11141329]
[http://dx.doi.org/10.4049/jimmunol.180.5.3132] [PMID: 18292536]
[PMID: 11888921]
[http://dx.doi.org/10.1084/jem.20101158] [PMID: 21930769]
[http://dx.doi.org/10.1016/j.ijrobp.2003.09.012] [PMID: 14967443]
[http://dx.doi.org/10.1200/JCO.2006.05.9964] [PMID: 16648493]
[http://dx.doi.org/10.1016/j.semcancer.2017.12.007] [PMID: 29258856]
[http://dx.doi.org/10.1084/jem.173.4.1017] [PMID: 2007850]
[http://dx.doi.org/10.1016/j.ccell.2017.06.009] [PMID: 28810142]
[http://dx.doi.org/10.1080/2162402X.2017.1346766] [PMID: 29123961]
[http://dx.doi.org/10.1007/s00262-013-1506-7] [PMID: 24357146]
[http://dx.doi.org/10.1158/0008-5472.CAN-10-2820] [PMID: 21300764]
[http://dx.doi.org/10.1038/s41591-018-0053-3] [PMID: 29867230]
[http://dx.doi.org/10.1002/adma.201802228] [PMID: 30663118]
[http://dx.doi.org/10.1016/j.ccr.2005.07.014] [PMID: 16098459]
[http://dx.doi.org/10.3109/0284186X.2014.939298] [PMID: 25140860]
[http://dx.doi.org/10.1080/02841860600954875] [PMID: 16982552]
[http://dx.doi.org/10.1016/j.ijrobp.2014.05.202]