Roles of V-domain Ig suppressor of T-cell activation-mediated immunoregulation in tumor immune escape (Review).

V-domain Ig suppressor of T-cell activation (VISTA), a key member of the B7 family of immune checkpoint molecules, exerts regulatory effects on T-cell function both directly and indirectly, thus serving a notable role in tumor immune evasion. VISTA directly inhibits the phosphorylation of key molecules in the T-cell receptor signaling pathway, leading to a reduction in the expression levels of pro-inflammatory factors within the tumor microenvironment (TME) and the establishment of an immunosuppressive TME. Furthermore, VISTA can indirectly modulate T-cell function by regulating various immune cells, including dendritic cells, macrophages and myeloid-derived suppressor cells. Targeting VISTA can effectively restore T-cell metabolic function, with monoclonal antibodies against VISTA exhibiting notable potential in the treatment of patients with PD-1 resistance. Several inhibitors (e.g., CI-8993 and SNS-101) targeting VISTA have already entered phase I/II clinical trials. Through its dual mechanisms of directly inhibiting T-cell activation and indirectly modulating the TME, VISTA constitutes a key component of tumor immune evasion, offering a vital target for cancer immunotherapy.