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

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.