VISTA Is an Immune Checkpoint Molecule for Human T Cells

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

    Research output: Contribution to journalArticlepeer-review

    362 Citations (Scopus)

    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.
    Original languageEnglish
    Pages (from-to)1924-1932
    JournalCancer Research
    Volume74
    Issue number7
    Early online date1 Apr 2014
    DOIs
    Publication statusPublished - 1 Apr 2014

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