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Distinct tissue niches contribute to prostate TRM cell differentiation and heterogeneity [Spatial Transcriptomics]

ABSTRACT: The prostate is an important exocrine organ, a barrier tissue of the male reproductive system, and a common site of malignancy, yet prostate CD8+ T cells remain largely uncharacterized. Here, we show that a protective, heterogeneous pool of long-lived, tissue-resident memory CD8+ T (Trm) cells forms in the prostate following acute infection in mice. Characterization of prostate Trm cell differentiation over time and functional interrogation of cytokine TGFβ-, IL-7-, and IL-15 signaling revealed niche-dependent phenotypic and functional diversity arising from distinct prostate stromal and glandular epithelial niches in both mice and humans. For instance, the Trm-promoting cytokines IL-15 and TGFβ were highest in the prostate epithelium, where CD8+ T cells were most persistent, cytotoxic, and enriched for the Trm molecular program. In sum, we provide a spatial framework for prostate Trm cell differentiation, charting discrete tissue regions that influence T cell fate through dynamic regulation of localized signals.

ORGANISM(S): Mus musculus

PROVIDER: GSE296275 | GEO | 2026/03/31

REPOSITORIES: GEO

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Distinct tissue niches contribute to prostate TRM cell differentiation and heterogeneity [scRNA-seq]

Project description:The prostate is an important exocrine organ, a barrier tissue of the male reproductive system, and a common site of malignancy, yet prostate CD8+ T cells remain largely uncharacterized. Here, we show that a protective, heterogeneous pool of long-lived, tissue-resident memory CD8+ T (Trm) cells forms in the prostate following acute infection in mice. Characterization of prostate Trm cell differentiation over time and functional interrogation of cytokine TGFβ-, IL-7-, and IL-15 signaling revealed niche-dependent phenotypic and functional diversity arising from distinct prostate stromal and glandular epithelial niches in both mice and humans. For instance, the Trm-promoting cytokines IL-15 and TGFβ were highest in the prostate epithelium, where CD8+ T cells were most persistent, cytotoxic, and enriched for the Trm molecular program. In sum, we provide a spatial framework for prostate Trm cell differentiation, charting discrete tissue regions that influence T cell fate through dynamic regulation of localized signals.

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Distinct tissue niches contribute to prostate TRM cell differentiation and heterogeneity [RNA-seq]

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