title: VISTA is an inhibitory immune checkpoint that is increased after ipilimumab therapy in patients with prostate cancer.
abstract: To date, anti-CTLA-4 (ipilimumab) or anti-PD-1 (nivolumab) monotherapy has not been demonstrated to be of substantial clinical benefit in patients with prostate cancer. To identify additional immune-inhibitory pathways in the prostate-tumor microenvironment, we evaluated untreated and ipilimumab-treated tumors from patients in a presurgical clinical trial. Levels of the PD-L1 and VISTA inhibitory molecules increased on independent subsets of macrophages in treated tumors. Our data suggest that VISTA represents another compensatory inhibitory pathway in prostate tumors after ipilimumab therapy.
authors.affiliation: Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Urology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: Ward
authors.affiliation: Department of Urology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Curtis A
authors.initials: CA
authors.lastname: Pettaway
authors.affiliation: Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Lewis Z
authors.initials: LZ
authors.lastname: Shi
authors.affiliation: Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Sumit K
authors.initials: SK
authors.lastname: Subudhi
authors.affiliation: The Immunotherapy Platform, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Vence
authors.affiliation: The Immunotherapy Platform, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Chen
authors.affiliation: The Immunotherapy Platform, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Eleni
authors.initials: E
authors.lastname: Efstathiou
authors.affiliation: Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Troncoso
authors.affiliation: The Immunotherapy Platform, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: Allison
authors.affiliation: Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Logothetis
authors.affiliation: Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Ignacio I
authors.initials: II
authors.lastname: Wistuba
authors.affiliation: Janssen Oncology Therapeutic Area, Janssen Research and Development, LLC, Pharmaceutical Companies of Johnson &Johnson, Spring House, Pennsylvania, USA.
authors.forename: Manuel A
authors.initials: MA
authors.lastname: Sepulveda
authors.affiliation: The Immunotherapy Platform, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wargo
authors.affiliation: The Immunotherapy Platform, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Jorge
authors.initials: J
authors.lastname: Blando
authors.affiliation: Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|The Immunotherapy Platform, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Padmanee
authors.initials: P
authors.lastname: Sharma
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D060887:B7 Antigens / Q000276:immunology / Q000378:metabolism*; D060890:B7-H1 Antigen / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D000074324:Ipilimumab; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes; D046888:Tissue Array Analysis
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060887:B7 Antigens; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C498919:Cd274 protein, mouse; D000074324:Ipilimumab; D008565:Membrane Proteins; C000588758:VSIR protein, human; C548983:Vsir protein, mouse