Disruption of the immune-checkpoint VISTA gene imparts a proinflammatory phenotype with predisposition to the development of autoimmunity

Significance The discovery of V domain-containing Ig suppressor of T-cell activation (VISTA) as a novel immune-checkpoint regulator comes at an exciting time, as the field of cancer immunotherapy has made significant progress owing to the clinical success of targeting immune-checkpoint proteins such as cytotoxic T lymphocyte-associated antigen 4 and programmed death 1 and ligand. Recent studies also show the promise of monoclonal antibody-mediated VISTA targeting for enhancing antitumor immunity in murine tumor models. The current study demonstrates the spectrum of immune alterations upon genetic disruption of VISTA in mice in the context of self-tolerance as well as immune response against neoantigen. These results enhance the understanding of the immune-regulatory role of VISTA and form the foundation for designing future clinical applications that target VISTA in treating human diseases.