VISTA: bridging gaps in cancer immunotherapy

Tumor microenvironment (TME) is complicated by the interaction of different cells of immune system, stromal components, and tumor-associated elements. Immune cells largely influence tumor progression by the means of various activating and inhibitory mechanisms including, immune checkpoint molecules. These molecules have been targeted for treating different types of cancers. For instance, blocking antibodies against CTLA-4, PD-1, or PD-L1 have elicited durable clinical responses and remarkable efficacy. These antibodies have also led to long-term remissions in a subset of patients, especially when used in combination therapies. V-domain immunoglobulin suppressor of T cell activation (VISTA) as a negative regulator of the immune system is expressed on multiple immune cell subsets including, myeloid-derived suppressor cells (MDSCs), macrophages, and lymphocytes. VISTA exerts regulatory effects and modulates T cell function and has shown prognostic significance in different cancers, leading to an increased attention regarding its suppressive role in the context of cancer. In this review, we will summarize the VISTA structure, ligands, role in the TME, and expression on immune cells. Furthermore, the significance of VISTA expression in the prognosis of cancer and its role in cancer immunotherapy, tumor resistance and ongoing clinical trials will be discussed.