Immune evasion in renal cell carcinoma: biology, clinical translation, future directions

Targeted therapies and immune checkpoint inhibitors have advanced the treatment landscape of Renal Cell Carcinoma (RCC) over last decade. While demonstrated survival benefit are currently approved in front-line second-line settings, primary secondary resistance is common. A comprehensive understanding mechanisms evasion RCC therefore critical to development effective combination strategies. This article reviews current different, yet coordinated, adopted by cells evade killing; summarizes various aspects clinical translation thus far, including registered trials exploring agents with inhibitors; provides perspectives on future directions for field. Clear cell renal carcinoma (ccRCC) accounts a large majority (?75%–80%) all RCC.1Shenoy N. Pagliaro L. Sequential pathogenesis metastatic VHL mutant clear carcinoma: putting it together translational perspective.Ann Oncol. 2016; 27: 1685-1695Abstract Full Text PDF PubMed Scopus (40) Google Scholar Non–clear (nccRCC) includes papillary, chromophobe, collecting duct, unclassified, translocation carcinomas. In 1990s, when interleukin-2 (IL-2) interferon (IFN)-? were studied cancer, selection criteria did not limit patients histology.2Atkins M.B. Sparano J. Fisher R.I. et al.Randomized phase II trial high-dose either alone or alfa-2b carcinoma.J Clin 1993; 11: 661-670Crossref (193) Scholar,3Fyfe G. Rosenberg S.A. al.Results 255 who received recombinant therapy.J 1995; 13: 688-696Crossref (1107) Over past 2 decades, however, after Heidelberg classification tumors4Kovacs Akhtar M. Beckwith B.J. al.The tumours.J Pathol. 1997; 183: 131-133Crossref (1136) starting randomized study investigating versus low-dose IL-2 RCC,5Yang J.C. Sherry R.M. 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