The structure, expression, and multifaceted role of immune-checkpoint protein VISTA as a critical regulator of anti-tumor immunity, autoimmunity, and inflammation

摘要

Among various immunoregulatory molecules,the B7 family of immune-checkpoint receptors consists of highly valuable targets for cancer immunotherapy.Antibodies targeting two B7 family co-inhibitory receptors,CTLA-4 and PD-1,have elicited long-term clinical outcomes in previously refractory cancer types and are considered a breakthrough in cancer therapy.Despite the success,the relatively low response rate(20–30%)warrants efforts to identify and overcome additional immune-suppressive pathways.Among the expanding list of T cell inhibitory regulators,V domain immunoglobulin suppressor of T cell activation(VISTA)is a unique B7 family checkpoint that regulates a broad spectrum of immune responses.Here,we summarize recent advances that highlight the structure,expression,and multi-faceted immunomodulatory mechanisms of VISTA in the context of autoimmunity,inflammation,and anti-tumor immunity.