Faculty Collaboration Database

VISTA is an immune checkpoint molecule for human T cells. Cancer Res 2014 Apr 01;74(7):1924-32

Date

04/03/2014

Pubmed ID

24691993

Pubmed Central ID

PMC3979527

DOI

10.1158/0008-5472.CAN-13-1504

Scopus ID

2-s2.0-84897445677 (requires institutional sign-in at Scopus site)   444 Citations

Abstract

V-domain Ig suppressor of T cell activation (VISTA) is a potent negative regulator of T-cell function that is expressed on hematopoietic cells. VISTA levels are heightened within the tumor microenvironment, in which its blockade can enhance antitumor immune responses in mice. In humans, blockade of the related programmed cell death 1 (PD-1) pathway has shown great potential in clinical immunotherapy trials. Here, we report the structure of human VISTA and examine its function in lymphocyte negative regulation in cancer. VISTA is expressed predominantly within the hematopoietic compartment with highest expression within the myeloid lineage. VISTA-Ig suppressed proliferation of T cells but not B cells and blunted the production of T-cell cytokines and activation markers. Our results establish VISTA as a negative checkpoint regulator that suppresses T-cell activation, induces Foxp3 expression, and is highly expressed within the tumor microenvironment. By analogy to PD-1 and PD-L1 blockade, VISTA blockade may offer an immunotherapeutic strategy for human cancer.

Author List

Lines JL, Pantazi E, Mak J, Sempere LF, Wang L, O'Connell S, Ceeraz S, Suriawinata AA, Yan S, Ernstoff MS, Noelle R

MESH terms used to index this publication - Major topics in bold

Animals
B7 Antigens
B7-H1 Antigen
Female
Humans
Immunoglobulins
Lymphocyte Activation
Mice
Mice, Inbred C57BL
T-Lymphocytes