“…(B): Immunomodulatory targets for tyrosine kinase inhibitors (TKIs)—rationale for combination with checkpoint inhibitors in RCC. TKIs have been shown, generally in ex vivo or non‐VHL tumor models, to modulate (suppress [red line] or stimulate [green arrow]) the activity of immune cells (e.g., activation, migration, proliferation, expansion, recruitment) involved in the tumor‐immune response, including CD8+ T cells , CD4+ T cells , T reg cells , APC , tumor‐associated macrophages , MDSC , and NK cells . Abbreviations: APC, antigen‐presenting cell; CD, cluster of differentiation; CTLA‐4, cytotoxic T‐lymphocyte‐associated protein 4; FGF, fibroblast growth factor; FGFR, fibroblast growth factor receptor; GAS6, AXL receptor tyrosine kinase ligand; HGF, hepatocyte growth factor; HIFα, hypoxia‐inducible factor alpha; IL‐10, interleukin 10; MDSC, myeloid‐derived suppressor cell; MHC, major histocompatibility complex; mTOR, mechanistic target of rapamycin; NK, natural killer; PD‐1, programmed cell death receptor 1; PDGF, platelet‐derived growth factor; PDGFR, platelet‐derived growth factor receptor; PD‐L1/L2, programmed cell death‐ligand 1 or 2; TCR, T‐cell receptor; T eff , effector T cell; TGF‐β, transforming growth factor‐β; T reg cell, regulatory T cell; VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptors; VHL, von Hippel‐Lindau.…”