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Medline ® Abstract for Reference 52

of 'Principles of cancer immunotherapy'

VISTA is an immune checkpoint molecule for human T cells.
Lines JL, Pantazi E, Mak J, Sempere LF, Wang L, O'Connell S, Ceeraz S, Suriawinata AA, Yan S, Ernstoff MS, Noelle R
Cancer Res. 2014 Apr;74(7):1924-32.
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 offeran immunotherapeutic strategy for human cancer.
Authors' Affiliations: Medical Research Council Centre of Transplantation, Guy's Hospital, King's College London, King's Health Partners; Department of Immune Regulation and Intervention, King's College London, London, United Kingdom; Department of Medicine, Geisel School of Medicine at Dartmouth; Department of Microbiology and Immunology, Dartmouth Medical School; and Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.