Immune Response Role of Angiogenesis Inhibitors

Abstract

Angiogenesis plays an important role in tumor growth. Established vasculature provides a supply of nutrients and other necessary survival factors for tumor cell maintenance. In addition, immune factors with capacity to both decrease immune activity leading to cancer suppression and to increase anticancer response are provided via VEGF stimulated angiogenesis. However, VEGF provides more than angiogenesis stimulation; it is itself a growth factor with activity to also decrease the stimulation of dendritic cells (DCs) and T cells involved in anti-cancer mechanisms. As such inhibition of VEGF provides immune therapeutic advantage. This was well demonstrated by IFN-ɣ ELISPOT assay in which T lymphocytes antitumor response was measured against multiple myeloma cells following exposure to myeloma lysate-loaded dendric cells. Block of VEGF lead to enhanced T lymphocyte anticancer immune response. Through stimulation of the immune system angiogenesis inhibitors can work in conjunction with immunotherapy, chemotherapy and/or radiation therapy. Recent clinical trials in advanced renal cell carcinoma, non-small cell lung cancer (NSCLC), and hepatocellular carcinoma have evidenced improved outcomes due to an immune enhancing effect with angiogenesis inhibition and in particular immune checkpoint blockade treatment.