Normalization of tumor vasculature: A potential strategy to increase the efficiency of immune checkpoint blockades in cancers

Immune checkpoint inhibitors (ICIs) eliminate tumor cells by reactivating CD8 + T cells using the cytotoxic effects of the immune system. However, in this process, tumor angiogenic factors and abnormal formation of tumor blood vessels are not conducive to the treatment of ICIs. In the tumor microenvironment (TME), proangiogenic factors prevent dendritic cell maturation, reduce T cell infiltration, and recruit inhibitory immune cells such as regulatory T (Treg) cells. Abnormal tumor blood vessels also prevent immune cells and chemotherapy drugs from reaching the target effectively and lead to poor perfusion and severe hypoxia of the tumor. Treatment with antiangiogenic inhibitors can block the transmission of abnormal angiogenesis signals and promote the normalization of tumor vasculature. Therefore, the combination of antiangiogenic inhibitors and ICIs is used in clinical therapy. Combination therapy has been proven theoretically feasible in preclinical trials, and many clinical trials have been completed to confirm its safety and efficacy.