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.
MeSH terms
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Adenocarcinoma / drug therapy*
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Adenocarcinoma / immunology
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Adenocarcinoma / metabolism
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Adult
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Aged
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Animals
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Antibodies, Monoclonal / therapeutic use*
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Antineoplastic Agents / therapeutic use*
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B7 Antigens / immunology
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B7 Antigens / metabolism*
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B7-H1 Antigen / immunology
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B7-H1 Antigen / metabolism*
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Cell Line, Tumor
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Disease Models, Animal
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Flow Cytometry
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Fluorescent Antibody Technique
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Humans
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Immunohistochemistry
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In Vitro Techniques
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Ipilimumab
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Macrophages / immunology
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Macrophages / metabolism*
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Male
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Membrane Proteins / immunology
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Membrane Proteins / metabolism
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Mice
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Middle Aged
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Neoadjuvant Therapy
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Prostatectomy
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Prostatic Neoplasms / drug therapy*
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Prostatic Neoplasms / immunology
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Prostatic Neoplasms / metabolism
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T-Lymphocytes
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Tissue Array Analysis
Substances
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Antibodies, Monoclonal
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Antineoplastic Agents
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B7 Antigens
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B7-H1 Antigen
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CD274 protein, human
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Cd274 protein, mouse
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Ipilimumab
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Membrane Proteins
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VSIR protein, human
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Vsir protein, mouse