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VISTA Is an Immune Checkpoint Molecule for Human T Cells

Research output: Contribution to journalArticle

J Louise Lines, Eirini Pantazi, Justin Mak, Lorenzo F Sempere, Li Wang, Samuel O'Connell, Sabrina Ceeraz, Arief A Suriawinata, Shaofeng Yan, Marc S Ernstoff, Randolph Noelle

Original languageEnglish
Article numberN/A
Pages (from-to)1924-1932
Number of pages9
JournalCancer Research
Volume74
Issue number7
DOIs
Publication statusPublished - 1 Apr 2014

King's Authors

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.

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