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We analyzed transcriptomic data from 487 TCGA\u2010PRAD patients and three Gene Expression Omnibus datasets; weighted gene co\u2010expression network analysis was used to identify cancer\u2010related genes, TIMER to evaluate their influence on the tumor microenvironment, and findings were validated via flow cytometry on 32 clinical PCa specimens. Immunoblotting measured Nrf2, p\u2010AKT, and p\u2010GSK\u20103\u03b2 levels, while ChIP\u2010qPCR assessed Nrf2 and RNA polymerase II binding to the\n                    <jats:italic>CX3CL1<\/jats:italic>\n                    promoter, and functional studies were conducted in allograft and xenograft mouse models using GapmeR antisense oligonucleotides combined with anti\u2010PD\u20101 antibodies or PSMA\u2010targeted CAR\u2010T cells. We found PPP1R14B (PP1 regulatory inhibitor subunit 14B) was overexpressed in PCa and associated with poor prognosis, promoting PCa cell proliferation, suppressing apoptosis, and correlating with increased tumor purity but reduced CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell infiltration; mechanistically, CX3CL1 was regulated by Nrf2 and PPP1R14B elevated p\u2010AKT\/p\u2010GSK\u20103\u03b2 to stabilize Nrf2, which bound the\n                    <jats:italic>CX3CL1<\/jats:italic>\n                    promoter, suppressed its expression, and impaired CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell chemotaxis. GapmeR\u2010mediated\n                    <jats:italic>PPP1R14B<\/jats:italic>\n                    knockdown suppressed tumor growth and enhanced anti\u2010PD\u20101\/CAR\u2010T efficacy in mice, indicating PPP1R14B is a promising target to overcome PCa immunotherapy resistance. \u00a9 2026 The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.70133","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T03:15:11Z","timestamp":1790133311000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting\n                    <scp>PPP1R14B<\/scp>\n                    overcomes immunotherapy resistance in prostate cancer by restoring\n                    <scp>CD8<\/scp>\n                    <sup>+<\/sup>\n                    T\u2010cell infiltration via the Nrf2\/\n                    <scp>CX3CL1<\/scp>\n                    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