Dual VEGF and PD-(L)1 Blockade: Facts and Hopes

VEGF-A/VEGF-R axis is well recognized for its role in tumor angiogenesis as well as tumor-induced immunosuppressive mechanisms. Targeting this pathway can help to switch tumor microenvironment toward a more immune-permissive state. Inhibition of VEGF-A/VEGFR has emerged as a strategy to enhance the efficacy of immunotherapy in some cancers leading to the approval of anti-VEGF-A/anti-PD(L)1 combinations in advanced renal cell cancer, hepatocellular carcinoma, non-small cell lung cancer, and endometrial cancer. However, in other tumor types, and particularly in colorectal cancer or glioblastoma, results remain limited. In this review, we discuss the biological rationale underlying anti-VEGF-A/PD-(L)1 combinations, summarize the clinical evidence supporting their use across tumor types, discuss the disappointing results in colorectal cancer and glioblastoma, and highlight emerging strategies to improve their therapeutic efficacy.