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Single-cell RNA-sequencing of BCG naïve and recurrent non-muscle invasive bladder cancer reveals a CD6/ALCAM-mediated immune-suppressive pathway

GSE269877 Homo sapiens Expression profiling by high throughput sequencing 38 samples Submitted 2025/08/12 Platform GPL20795
Summary
Bacillus Calmette-Guérin (BCG) is the mainstay of treatment for intermediate- and high-risk non-muscle invasive bladder cancer (NMIBC), yet recurrence rates remain high. To improve the efficacy of BCG, a better understanding of the immune landscape underlying BCG resistance is critical. Here, we performed single-cell RNA-sequencing (scRNA-seq) and whole-exome sequencing on tumors from NMIBC patients before and after BCG treatment. Our analysis revealed a marked increase in CD6/ALCAM interactions between T cells and urothelial cells in BCG recurrent tumors. CD6-high T cells were enriched in recurrent tumors and exhibited downregulation of activation-related genes, indicative of functional impairment. These observations were supported by analysis of an independent BCG-treated NMIBC cohort, in which CD6/ALCAM signaling was correlated with shorter recurrence-free survival (p = 0.00059). Our findings reveal a previously unrecognized association between CD6/ALCAM signaling and BCG resistance in NMIBC patients and highlight this pathway as a potential therapeutic target to enhance response to BCG.
Published in
Single-cell RNA-sequencing of BCG naïve and recurrent non-muscle invasive bladder cancer reveals a CD6/ALCAM-mediated immune-suppressive pathway
Juric I, Fink EE, Qiu H et al. · NPJ precision oncology 2025 · PMID 41006678 · doi:10.1038/s41698-025-01093-3
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Direct links to NCBI, no account and no request form: the whole study as GSE269877_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 38 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1039857. Searching any of these in the dataset finder brings you back here.

Study design
38 conditions, each sampled once — no replicated groups

Read from 38 sample titles: 38 distinct titles with little repetition. Check it against the sample list below before relying on it.

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