CXCR6 expression predicts prognosis and immunotherapeutic benefit in muscle-invasive bladder cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39588301", "kind": "science-record", "revision": 2, "content_hash": "sha256:96086b25dc05a434250f6cf687803e57b121ac2a32e19ba52ba6765645b27ab7", "created_at": "2026-11-01T20:29:51Z", "updated_at": "2026-11-01T21:34:24Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "CXCR6 expression predicts prognosis and immunotherapeutic benefit in muscle-invasive bladder cancer.", "doi": "10.3389/fonc.2024.1498579", "pmid": "39588301", "authors": ["Xiaolin Lu", "Li-Ping Ge", "Zhaopei Liu", "Yu Zhu", "Dingwei Ye", "Yuan Chang"], "journal": "Frontiers in oncology", "year": 2024, "abstract": "Background: Increasing evidence suggests that the CXC chemokine receptor 6 (CXCR6) is involved in tumor progression and the regulation of tumor immunity. However, its role in muscle-invasive bladder cancer (MIBC) remains largely unexplored.\nMethods: Data from 391 MIBC patients in the TCGA, 212 patients from GEO, 131 patients from our center, 195 patients in the IMvigor210 cohort, and single-cell RNA sequencing (scRNA-seq) data from 9 bladder cancer patients (GSE222315) were analyzed. Additionally, data from the GEPIA 2, TISCH2, TIMER2.0, and UALCAN platforms were utilized to investigate the prognostic and immunotherapeutic significance of CXCR6 in MIBC.\nResults: We observed that CXCR6 expression was significantly reduced in bladder cancer tumors and correlated with tumor stage and grade. Low CXCR6 expression was associated with poor recurrence-free survival (RFS) and overall survival (OS) in the TCGA cohort, a finding validated in both the meta-GEO dataset and our center's cohort. Multivariate analysis confirmed that low CXCR6 expression was an independent predictor of poor OS and RFS. A nomogram incorporating CXCR6 expression and other independent prognostic factors was developed to accurately predict 3- and 5-year OS. Gene set enrichment analysis indicated that immune activation-related pathways were significantly enriched in tumors with high CXCR6 expression. CIBERSORT analysis revealed that CXCR6 expression was positively correlated with CD8+ T cells, CD4+ T cells, activated NK cells, M1 macrophages, and activated dendritic cells in TCGA, findings further validated by TIMER2.0. scRNA-seq data showed that CXCR6 was predominantly expressed in T and NK cells and facilitated T/NK-myeloid interaction via the CXCR6-CXCL16 axis. Importantly, CXCL16+ macrophages and dendritic cells recruited CXCR6+ T and NK cells, which exhibited enhanced cytotoxicity, thereby amplifying anti-tumor immunity. Clinically, in the IMvigor210 immunotherapy cohort, higher CXCR6 expression was associated with improved anti-PD-L1 therapeutic outcomes.\nConclusion: Our findings highlight CXCR6 as a critical biomarker for predicting prognosis and immunotherapeutic response in MIBC.", "claims": [{"id": "claim-method", "statement": "Survival curves were analyzed using the Kaplan-Meier method and compared with log-rank tests.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39588301", "locator": "sections[10] \"Statistical analyses\" paragraph 2", "quote": "Survival curves were analyzed using the Kaplan-Meier method and compared with log-rank tests."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data presented in the study can be found in online repositories. The names of the repositories and accession numbers can be found in the article/ Supplementary Material . 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