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Rabadi et al. J Cancer Metastasis Treat 2022;8:24 Journal of Cancer
DOI: 10.20517/2394-4722.2022.06
Metastasis and Treatment

Review Open Access

The role of VISTA in the tumor microenvironment

1
2
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Dina Rabadi , Alia A. Sajani , Randolph J. Noelle , J. Louise Lines 2
1
Department of Biological Sciences, Dartmouth College, Hanover, NH 03755, USA.
2
Department of Microbiology and Immunology, Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon,
NH 03756, USA.
Correspondence to: Dr. Randolph J. Noelle, Department of Microbiology and Immunology, Norris Cotton Cancer Center, Geisel
School of Medicine at Dartmouth, Lebanon, NH 03756, USA. E-mail: randolph.j.noelle@dartmouth.edu
How to cite this article: Rabadi D, Sajani AA, Noelle RJ, Lines JL. The role of VISTA in the tumor microenvironment. J Cancer
Metastasis Treat 2022;8:24. https://dx.doi.org/10.20517/2394-4722.2022.06

Received: 13 Jan 2022 First Decision: 10 Mar 2022 Revised: 15 Apr 2022 Accepted: 29 Apr 2022 Published: 22 Jun 2022

Academic Editors: Steven Fiering, Silvana Morello Copy Editor: Fangling Lan Production Editor: Fangling Lan

Abstract
V-domain Ig Suppressor of T cell Activation (VISTA) is a negative immune checkpoint that is expressed on
multiple immune cell subsets and has been characterized in T cells, macrophages, and myeloid-derived suppressor
cells. As the only immune checkpoint expressed on naïve T cells, VISTA contributes to the maintenance of T cell
quiescence and tolerance. VISTA also regulates multiple myeloid cell activities such as chemotaxis, differentiation,
and migration. In the context of cancer, antagonistic monoclonal antibody targeting of VISTA has been shown to
aid anti-tumor immunity. Furthermore, combination therapies that include other immune checkpoints such as PD-1
or CTLA-4 with VISTA blockade may enhance therapeutic efficacy in a variety of cancers. Combination therapy
may help overcome adaptive resistance to individual checkpoint therapies, thereby improving patient outcomes
and survival. Here, we summarize the role of VISTA in myeloid cells and T cells within the tumor
microenvironment. We discuss the proposed counter-receptors for VISTA, VISTA antibodies currently in
development, and the potential for combination therapies with checkpoint inhibitors such as PD-1 and CTLA-4.
Keywords: VISTA, cancer, MDSC, immune checkpoint

INTRODUCTION
While cancer mortality rates have decreased over the past several decades due to the classic cancer
treatment approaches (chemotherapy, radiation, and surgery), incidence rates continue to climb and are

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0
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