VISTA: A novel immunotherapy target for normalizing innate and adaptive immunity

•We discuss the role of VISTA as a negative checkpoint directing both innate and adaptive immunity.•VISTA is broadly expressed on myeloid and T cells, and increases with tumor progression.•VISTA is a unique target with both antagonistic and agonistic antibodies available.•VISTA presents an attractive target for cancer immunotherapy with preclinical studies showing promising outcomes of anti-VISTA in multiple models. V-domain Ig suppressor of T cell activation (VISTA) is a novel checkpoint regulator with limited homology to other B7 family members. The constitutive expression of VISTA on both the myeloid and T lymphocyte lineages coupled to its important role in regulating innate and adaptive immune responses, qualifies VISTA to be a promising target for immunotherapeutic intervention. Studies have shown differential impact of agonistic and antagonistic targeting of VISTA, providing a unique landscape for influencing the outcome of cancer and inflammatory diseases.