VISTA: A Promising Target for Cancer Immunotherapy?

Abstract

Abstract Agents targeting the B7 family co-inhibitory receptors cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein-1 (PD-1), or its ligand (PD-L1), have a pivotal role in clinical practice. V-domain Ig suppressor of T-cell activation (VISTA) is a protein highly conserved between species, with a similar amino acid sequence to the B7 family members, characterized by a particularly structural homology to PD-1. It has been counted as an emerging target within the list of novel targetable immune checkpoints in oncology. Physiologically, VISTA exerts a regulatory function on the immune system at several levels, particularly by modulating T cells activation. Its altered activity plays a role in many autoimmune diseases, and its expression has been found to be prognostically implicated in different cancer types in preclinical models. We hereby present the main evidence on the value of VISTA as an immune checkpoint in solid and hematological malignancies. We also review its value as a potential target for cancer immunotherapy, by reporting the results of Phase I and II clinical trials assessing the use of drugs targeting VISTA. The complexity of its pathway, along with some unclear biological aspects concerning its molecular interactions, currently represent a limit to the applicability of VISTA as an effective biomarker for immunotherapy in oncology. A deeper characterization of this immune checkpoint may help defining its value within immune signatures of solid and hematological malignancies, and to design future therapeutic strategies.