title: VISTA is an immune checkpoint molecule for human T cells.
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.
authors.affiliation: 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.
authors.forename: J Louise
authors.initials: JL
authors.lastname: Lines
authors.forename: Eirini
authors.initials: E
authors.lastname: Pantazi
authors.forename: Justin
authors.initials: J
authors.lastname: Mak
authors.forename: Lorenzo F
authors.initials: LF
authors.lastname: Sempere
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Samuel
authors.initials: S
authors.lastname: O'Connell
authors.forename: Sabrina
authors.initials: S
authors.lastname: Ceeraz
authors.forename: Arief A
authors.initials: AA
authors.lastname: Suriawinata
authors.forename: Shaofeng
authors.initials: S
authors.lastname: Yan
authors.forename: Marc S
authors.initials: MS
authors.lastname: Ernstoff
authors.forename: Randolph
authors.initials: R
authors.lastname: Noelle
mesh_terms: D000818:Animals; D060887:B7 Antigens / Q000737:chemistry / Q000502:physiology*; D060890:B7-H1 Antigen; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D060887:B7 Antigens; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D007136:Immunoglobulins; C000588758:VSIR protein, human