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As central effectors of antitumor immunity, the extent of CD8\u2009+\u2009T cell infiltration into tumors is a key determinant of immunotherapy response. Members of the histone deacetylase (HDAC) family play critical roles in modulating tumor immune evasion and sensitivity to immunotherapy, making HDAC inhibitors of clinical interest.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A retrospective analysis was performed using data from the IMvigor210 clinical trial and follow-up data from patients with locally advanced BCa who received adjuvant immunotherapy at our center, assessing the association between HDAC1\u201311 expression and immunotherapy response. RNA sequencing, gene set enrichment analysis (GSEA), chromatin immunoprecipitation PCR (ChIP-PCR), co-immunoprecipitation (Co-IP), mass spectrometry, lysine site mutagenesis, RNA immunoprecipitation, and bioinformatics analysis were employed to outline the HDAC7\u2013BTRC\u2013SRSF7\u2013CCL5 pathway. The immunoregulatory function of HDAC7 was evaluated using CD8\u2009+\u2009T cell co-culture assays and tumor models in humanized NOG (HuNOG) mice. Virtual screening, MicroScale Thermophoresis (MST), and HDAC activity assays were conducted to identify potential HDAC7 specific inhibitor. The immunosensitizing effect of Pinocembrin on BCa immunotherapy was validated using a C57BL\/6 mouse tumor-bearing model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among the HDAC family members, only HDAC7 expression was significantly associated with immunotherapy response. HDAC7 was overexpressed in BCa and correlated with poorer prognosis. Functional assays demonstrated that HDAC7 suppresses CD8\u2009+\u2009T cell infiltration, thereby reducing sensitivity to PD-1 antibody treatment. Mechanistically, HDAC7 reduced acetylation at lysine 24 of the splicing regulator SRSF7, enhancing BTRC-mediated ubiquitination and degradation of SRSF7, which promoted the processing and expression of CCL5 mRNA-a chemokine essential for CD8\u2009+\u2009T cell recruitment. Furthermore, Pinocembrin was identified as a selective HDAC7 inhibitor that restores CD8\u2009+\u2009T cell infiltration and improves immunotherapy efficacy in BCa.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>HDAC7 represents a promising diagnostic and therapeutic target in BCa immunotherapy. Pinocembrin, as a specific HDAC7 inhibitor, holds potential as a combination therapy agent to improve immunotherapy response in BCa.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13046-025-03585-3","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T10:47:04Z","timestamp":1766573224000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Histone deacetylase HDAC7 restricts CD8\u2009+\u2009T cell tumor infiltration and limits immunotherapy sensitivity in bladder cancer: reversal by pinocembrin"],"prefix":"10.1186","volume":"44","author":[{"given":"Jiancheng","family":"Lv","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiatong","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruixi","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,24]]},"reference":[{"issue":"1","key":"3585_CR1","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1038\/s41572-023-00468-9","volume":"9","author":"L Dyrskj\u00f8t","year":"2023","unstructured":"Dyrskj\u00f8t L, Hansel DE, Efstathiou JA, Knowles MA, Galsky MD, Teoh J, et al. 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