VISTA: A Mediator of Quiescence and a Promising Target in Cancer Immunotherapy

V-domain Ig suppressor of T cell activation (VISTA) is a B7 family member that maintains T cell and myeloid quiescence and is a promising target for combination cancer immunotherapy. During inflammatory challenges, VISTA activity reprograms macrophages towards reduced production of proinflammatory cytokines and increased production of interleukin (IL)-10 and other anti-inflammatory mediators. The interaction of VISTA with its ligands is regulated by pH, and the acidic pH -6.0 in the tumor microenvironment (TME) facilitates VISTA binding to P-selectin glycoprotein ligand 1 (PSGL-1). Targeting intratumoral pH might be a way to reduce the immunoinhibitory activity of the VISTA pathway and enhance antitumor immune responses. We review differences among VISTA therapeutics under development as candidate immunotherapies, focusing on VISTA binding partners and the unique structural features of this interaction.

Automated summary

VISTA, a B7 family member, plays a role in maintaining immune cell quiescence and is a potential target for cancer immunotherapy. It reprograms macrophages and its interaction with ligands is regulated by pH, suggesting targeting intratumoral pH could enhance antitumor immune responses. Additionally, differences among VISTA therapeutics and their potential as candidate immunotherapies are being actively researched.