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VISTA is an inhibitory immune checkpoint that is increased after ipilimumab therapy in patients with prostate cancer
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VISTA is an inhibitory immune checkpoint that is increased after ipilimumab therapy in patients with prostate cancer
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Journal Article
VISTA is an inhibitory immune checkpoint that is increased after ipilimumab therapy in patients with prostate cancer
2017
Overview
Prostate cancer is refractory to anti-CTLA-4 therapy, but the reason why is unclear. Padmanee Sharma and colleagues report that the inhibitory molecule VISTA, which negatively regulates T cells, is upregulated on macrophages in prostate tumors that have been treated with anti-CTLA-4 and may play a role in resistance to this immunotherapy.
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.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ 82/51
/ Adenocarcinoma - drug therapy
/ Adult
/ Aged
/ Animals
/ Antibodies, Monoclonal - therapeutic use
/ Antineoplastic Agents - therapeutic use
/ Fluorescent Antibody Technique
/ Humans
/ Male
/ Membrane Proteins - immunology
/ Membrane Proteins - metabolism
/ Mice
/ Oncology
/ Prostatic Neoplasms - drug therapy
/ Prostatic Neoplasms - immunology
/ Prostatic Neoplasms - metabolism
/ Tumors
