First-line vascular endothelial growth factor targeted therapy in renal cell carcinoma: priming the tumor microenvironment for immunotherapy

Despite improved outcomes with systemic vascular endothelial growth factor (VEGF)-targeted agents in patients with advanced renal cell carcinoma (RCC), the majority of patients will eventually develop treatment resistance and disease progression. With the emergence of checkpoint inhibitors as potential treatment approaches, studies suggest that ideally combining or sequencing them with VEGF receptor (VEGFR)–tyrosine kinase inhibitors (TKIs) may provide more effective treatments that reduce or delay disease progression. Indeed, preliminary evidence suggests that VEGFR-TKIs can reverse immunosuppressive effects in the tumor microenvironment, potentially enhancing the effects of subsequent immunotherapy with checkpoint inhibitors. However, questions remain regarding the most effective treatment sequences or combinations with VEGFR-TKIs and checkpoint inhibitors. This review discusses the potential role of first-line VEGFR-TKIs in priming the tumor microenvironment for immunotherapy.