2. Academic Validation
  3. VISTA: A Mediator of Quiescence and a Promising Target in Cancer Immunotherapy

VISTA: A Mediator of Quiescence and a Promising Target in Cancer Immunotherapy

  • Trends Immunol. 2021 Mar;42(3):209-227. doi: 10.1016/j.it.2020.12.008.
Long Yuan 1,  Jahnavi Tatineni 2,  Kathleen M Mahoney 3,  Gordon J Freeman 4
Affiliations

Affiliations

  • 1 Program in Immunology, Harvard Medical School, Boston, MA 02115, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
  • 2 Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
  • 3 Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
  • 4 Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. Electronic address: gordon_freeman@dfci.harvard.edu.
PMID: 33495077 DOI: 10.1016/j.it.2020.12.008
Abstract

V-domain Ig suppressor of T cell activation (VISTA) is a B7 family member that maintains T cell and myeloid quiescence and is a promising target for combination Cancer Immunotherapy. During inflammatory challenges, VISTA activity reprograms macrophages towards reduced production of proinflammatory cytokines and increased production of interleukin (IL)-10 and Other anti-inflammatory mediators. The interaction of VISTA with its ligands is regulated by pH, and the acidic pH ~6.0 in the tumor microenvironment (TME) facilitates VISTA binding to P-selectin glycoprotein ligand 1 (PSGL-1). Targeting intratumoral pH might be a way to reduce the immunoinhibitory activity of the VISTA pathway and enhance antitumor immune responses. We review differences among VISTA therapeutics under development as candidate immunotherapies, focusing on VISTA binding partners and the unique structural features of this interaction.

Keywords

Acidic tumor microenvironment; Cancer immunotherapy; Immunosuppression; PSGL-1; VISTA; VSIG3.

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