title: VISTA is a novel broad-spectrum negative checkpoint regulator for cancer immunotherapy.
abstract: In the past few years, the field of cancer immunotherapy has made great progress and is finally starting to change the way cancer is treated. We are now learning that multiple negative checkpoint regulators (NCR) restrict the ability of T-cell responses to effectively attack tumors. Releasing these brakes through antibody blockade, first with anti-CTLA4 and now followed by anti-PD1 and anti-PDL1, has emerged as an exciting strategy for cancer treatment. More recently, a new NCR has surfaced called V-domain immunoglobulin (Ig)-containing suppressor of T-cell activation (VISTA). This NCR is predominantly expressed on hematopoietic cells, and in multiple murine cancer models is found at particularly high levels on myeloid cells that infiltrated the tumors. Preclinical studies with VISTA blockade have shown promising improvement in antitumor T-cell responses, leading to impeded tumor growth and improved survival. Clinical trials support combined anti-PD1 and anti-CTLA4 as safe and effective against late-stage melanoma. In the future, treatment may involve combination therapy to target the multiple cell types and stages at which NCRs, including VISTA, act during adaptive immune responses.
authors.affiliation: Authors' Affiliations: Medical Research Council Centre of Transplantation, Guy's Hospital; Department of Immune Regulation and Intervention, King's College, King's Health Partners, London, United Kingdom; Van Andel Research Institute, Grand Rapids, Michigan; Departments of Medicine and Microbiology and Immunology, and Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire; and Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WisconsinAuthors' Affiliations: Medical Research Council Centre of Transplantation, Guy's Hospital; Department of Immune Regulation and Intervention, King's College, King's Health Partners, London, United Kingdom; Van Andel Research Institute, Grand Rapids, Michigan; Departments of Medicine and Microbiology and Immunology, and Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire; and Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin rjn@dartmouth.edu janet.lines@kcl.ac.uk.
authors.forename: J Louise
authors.initials: JL
authors.lastname: Lines
authors.affiliation: Authors' Affiliations: Medical Research Council Centre of Transplantation, Guy's Hospital; Department of Immune Regulation and Intervention, King's College, King's Health Partners, London, United Kingdom; Van Andel Research Institute, Grand Rapids, Michigan; Departments of Medicine and Microbiology and Immunology, and Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire; and Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Lorenzo F
authors.initials: LF
authors.lastname: Sempere
authors.affiliation: Authors' Affiliations: Medical Research Council Centre of Transplantation, Guy's Hospital; Department of Immune Regulation and Intervention, King's College, King's Health Partners, London, United Kingdom; Van Andel Research Institute, Grand Rapids, Michigan; Departments of Medicine and Microbiology and Immunology, and Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire; and Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WisconsinAuthors' Affiliations: Medical Research Council Centre of Transplantation, Guy's Hospital; Department of Immune Regulation and Intervention, King's College, King's Health Partners, London, United Kingdom; Van Andel Research Institute, Grand Rapids, Michigan; Departments of Medicine and Microbiology and Immunology, and Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire; and Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Thomas
authors.initials: T
authors.lastname: Broughton
authors.affiliation: Authors' Affiliations: Medical Research Council Centre of Transplantation, Guy's Hospital; Department of Immune Regulation and Intervention, King's College, King's Health Partners, London, United Kingdom; Van Andel Research Institute, Grand Rapids, Michigan; Departments of Medicine and Microbiology and Immunology, and Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire; and Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Authors' Affiliations: Medical Research Council Centre of Transplantation, Guy's Hospital; Department of Immune Regulation and Intervention, King's College, King's Health Partners, London, United Kingdom; Van Andel Research Institute, Grand Rapids, Michigan; Departments of Medicine and Microbiology and Immunology, and Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire; and Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WisconsinAuthors' Affiliations: Medical Research Council Centre of Transplantation, Guy's Hospital; Department of Immune Regulation and Intervention, King's College, King's Health Partners, London, United Kingdom; Van Andel Research Institute, Grand Rapids, Michigan; Departments of Medicine and Microbiology and Immunology, and Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire; and Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WisconsinAuthors' Affiliations: Medical Research Council Centre of Transplantation, Guy's Hospital; Department of Immune Regulation and Intervention, King's College, King's Health Partners, London, United Kingdom; Van Andel Research Institute, Grand Rapids, Michigan; Departments of Medicine and Microbiology and Immunology, and Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire; and Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WisconsinAuthors' Affiliations: Medical Research Council Centre of Transplantation, Guy's Hospital; Department of Immune Regulation and Intervention, King's College, King's Health Partners, London, United Kingdom; Van Andel Research Institute, Grand Rapids, Michigan; Departments of Medicine and Microbiology and Immunology, and Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire; and Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WisconsinAuthors' Affiliations: Medical Research Coun
authors.forename: Randolph
authors.initials: R
authors.lastname: Noelle
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D060887:B7 Antigens / Q000037:antagonists & inhibitors; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors; D059447:Cell Cycle Checkpoints / Q000276:immunology; D004195:Disease Models, Animal; D005544:Forecasting; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D057285:Precision Medicine / Q000379:methods; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1 / Q000037:antagonists & inhibitors
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D060887:B7 Antigens; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C423237:CD276 protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C000588758:VSIR protein, human; C475826:VTCN1 protein, human