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. 2022 Dec 1;28(23):5013-5020.
doi: 10.1158/1078-0432.CCR-21-2372.

Facts and Hopes for Immunotherapy in Renal Cell Carcinoma

Chen Yao #  1   2 , Tian Zhang #  2   3 , Tuoqi Wu  1   4 , James Brugarolas  2   3
Affiliations

Facts and Hopes for Immunotherapy in Renal Cell Carcinoma

Chen Yao et al. Clin Cancer Res. .

Abstract

Immunotherapy has made a significant impact in many tumors, including renal cell carcinoma (RCC). RCC has been known to be immunoresponsive since the cytokine era of IFNα and IL2, but only a small number of patients had durable clinical benefit. Since then, discoveries of key tumor drivers, as well as an understanding of the contribution of angiogenesis and the tumor microenvironment (TME), has led to advances in drug development, ultimately transforming patient outcomes. Combinations of anti-angiogenic agents with immune checkpoint inhibitors are now standard of care. Current challenges include patient selection for immunotherapy combinations, resistance acquisition, and optimally sequencing therapies. Further discoveries about RCC biology, the TME, and resistance mechanisms will likely pave the way for the next generation of therapies.

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Conflict of interest statement

Conflict of interests: T. Zhang reports grants and personal fees from Genentech/Roche, Merck, Janssen, Pfizer, AstraZeneca, and SeaGen; grants from Novartis, Merrimack, AbbVie, Regeneron, Mirati Therapeutics, Omniseq, and PGDx; and personal fees from Exelixis, BMS, Sanofi-Aventis, Amgen, Dendreon, Eisai, Calithera, QED Therapeutics, Aveo, Bayer, Eli Lilly, MJH Associates, Peerview, Vaniam Group, Aptitude Health, PlatformQ, Integrity CE, and Aravive outside the submitted work. J. Brugarolas reports personal fees from Eisai, Johnson & Johnson, Exelixis, Arrowhead, and Calithera outside the submitted work. No disclosures were reported by the other authors.

Figures

Figure 1
Figure 1
Schematic overview of renal cell carcinoma with targeted immunotherapies. Top: Immune cell subsets and cytokines that shape the tumor microenvironment of RCC. Bottom: FDA approved drugs for RCC (bold) and their molecular targets. cDC, classical dendritic cells; CTLA-4, cytotoxic T-lymphocyte antigen 4; eIF4E, eukaryotic translation initiation factor 4E; FKBP12, FK506-binding protein 12; HIF1α, hypoxia inducible factor 1α; HIF2α, hypoxia inducible factor 2α; IL8, interleukin 8; IL10, interleukin 10; MDSC, myeloid-derived suppressor cells; MHC-1, major histocompatibility complex I; mTORC1, mammalian target of rapamycin complex 1; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; PDGFβ, platelet-derived growth factor β; PDGFRβ, platelet-derived growth factor receptor β; PTEN, phosphatase and tensin homologue; S6K, S6 kinase; TCR, T-cell receptor; TGFβ, transforming growth factor β; Treg, regulatory T cells; TSC1, tuberous sclerosis complex 1; TSC2, tuberous sclerosis complex 2; VEGF, vascular endothelial growth factor; VEGFR2, vascular endothelial growth factor receptor 2; VHL, von Hippel-Lindau.
See this image and copyright information in PMC

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