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Here, a CRISPR cas9 screening in vivo and an RNA-sequencing for clinical immunotherapy resistance BC samples identified enolase 1 (ENO1) as a potent regulator of anti-PD-L1 treatment efficacy. Investigation of clinical BC samples demonstrated a correlation between ENO1 overexpression and immune evasion in BC, evidenced by reduced CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell infiltration and resistance to anti-PD-L1 therapy. Increased CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell infiltration and function were indicative of antitumor immunity, which was elicited by ENO1 knockdown, which also suppressed carcinogenesis. Single-cell RNA sequencing demonstrated that wild-type (WT) and ENO1 knockout (KO) tumors have different immune cell compositions with the latter preferring an immunostimulatory microenvironment. Mechanistically, ENO1 regulated CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell function and tumor-associated macrophage (TAM) polarization via the SPP1-ITGA4\/ITGB1 pathway in the TME. Importantly, genetic and pharmacological inhibition of ENO1 sensitizes tumors to anti-tumor immunity and synergizes with anti-PD-L1 therapy. The results highlight tumor-intrinsic ENO1 as a critical regulator of tumor immune evasion in BC. Targeting ENO1 enhance the efficacy of immune checkpoint blockade therapy by promoting antitumor immunity.\n                  <\/jats:p>","DOI":"10.1186\/s13046-025-03464-x","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T06:06:14Z","timestamp":1752559574000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Tumor-intrinsic ENO1 inhibition promotes antitumor immune response and facilitates the efficacy of anti-PD-L1 immunotherapy in bladder cancer"],"prefix":"10.1186","volume":"44","author":[{"given":"Chengquan","family":"Shen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ding","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changxue","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8861-1003","authenticated-orcid":false,"given":"Yonghua","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,15]]},"reference":[{"key":"3464_CR1","doi-asserted-by":"publisher","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. 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This study was approved by the Affiliated Hospital of Qingdao University. Informed consent was obtained from all individual participants included in the study (QYFYWZLL28729). The ethical approval of animal experiments in our study was obtained from the Experimental Animal Welfare Ethics Committee of the Affiliated Hospital of Qingdao University (QYFYWZLL28730).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"207"}}