VISTA is a key driver of immunosuppression in the TME resulting in blockade and down-regulation of the immune response which are the hallmarks of a ‘‘cold tumor.’’

VISTA is a negative  immune checkpoint that suppresses T cell function in a variety of solid tumors. High VISTA expression in tumor correlates with poor survival in cancer patients and has been associated with a lack of response to other CPIs.

Blocking VISTA drives an efficient polyfunctional immune response to address immunosuppression and turn cold tumors hot. VISTA is a novel immuno-oncology target due to its unique expression and activity. First, high VISTA expression on myeloid cells (monocytes and macrophages) is consistent across tumor types, making it a relevant target across multiple types of cancer. Re-programmed monocytes can drive tumor inflammation. Releasing suppression of myeloid cells by targeting VISTA can provide single agent tumor growth inhibition and also improve efficacy of T cell focused therapies like anti-PD(L)1 and anti-CTLA4.

Second, blocking VISTA induces activation of dendritic cells and ultimately proliferation and infiltration of T cells into the tumor. The combination of myeloid and T cell responses can reverse immunosuppression and drive anti-tumor activity. While many immuno-oncology targets address either T cell or myeloid functions, VISTA has indicated the potential to regulate both.