{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T02:34:04Z","timestamp":1788402844563,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,3,29]],"date-time":"2023-03-29T00:00:00Z","timestamp":1680048000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Evading immune surveillance is a hallmark for the development of multiple cancer types. Whether immune evasion contributes to the pathogenesis of high\u2010grade prostate cancer\u00a0(HGPCa) remains an area of active inquiry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Through single\u2010cell RNA sequencing and multicolor flow cytometry of freshly isolated prostatectomy specimens and matched peripheral blood, we aimed to characterize the tumor immune microenvironment (TME)\u00a0of localized prostate cancer (PCa), including HGPCa\u00a0and low\u2010grade prostate cancer (LGPCa).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      HGPCa are highly infiltrated by exhausted CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, myeloid cells, and regulatory T cells (TRegs).\u00a0These HGPCa\u2010infiltrating CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells expressed high levels of exhaustion markers including TIM3, TOX, TCF7, PD\u20101, CTLA4, TIGIT, and CXCL13. By contrast, a high ratio of activated CD8\n                      <jats:sup>+<\/jats:sup>\n                      \u00a0effector T cells relative to TRegs and myeloid cells infiltrate the TME of LGPCa. HGPCa\u00a0CD8\n                      <jats:sup>+<\/jats:sup>\n                      \u00a0tumor\u2010infiltrating lymphocytes\u00a0(TILs) expressed more androgen receptor and prostate\u2010specific membran antigen yet less prostate\u2010specific antigen than the LGPCa CD8\n                      <jats:sup>+<\/jats:sup>\n                      \u00a0TILs. The PCa TME was infiltrated by macrophages but these did not clearly cluster by M1 and M2 markers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our study reveals a suppressive TME with high levels of CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell exhaustion in localized PCa, a finding enriched in HGPCa relative to LGPCa. These studies suggest a possible link between the clinical\u2010pathologic risk of PCa and the associated TME. Our results have implications for our understanding of the immunologic mechanisms of PCa pathogenesis and the implementation of immunotherapy for localized PCa.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pros.24524","type":"journal-article","created":{"date-parts":[[2023,3,29]],"date-time":"2023-03-29T10:17:24Z","timestamp":1680085044000},"page":"840-849","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Single\u2010cell analysis of localized prostate cancer patients links high Gleason score with an immunosuppressive profile"],"prefix":"10.1002","volume":"83","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4386-3490","authenticated-orcid":false,"given":"Victor R.","family":"Adorno Febles","sequence":"first","affiliation":[{"name":"Department of Medicine, Laura &amp; Isaac Perlmutter Cancer Center NYU Langone Health New York New York USA"},{"name":"Department of Medicine, Manhattan Campus VA NY Harbor Health Care System New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Hao","sequence":"additional","affiliation":[{"name":"Applied Bioinformatics Laboratories New York University Langone Health  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aarif","family":"Ahsan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Laura &amp; 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