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

Tissue-resident memory CD8+ T (TRM) cells directly kill infected cells and activate local immunity to limit reinfection. The prostate is an exocrine organ, a barrier tissue to the male reproductive system, and a site of malignancy, yet prostate TRM cells and the unique cues in the tissue environment remain unexplored. Prostate TRM cells protect against reinfection in a mouse model of acute infection and display functional and phenotypic heterogeneity in both mice and humans. We survey the prostate tissue using spatial transcriptomics and map features of TRM cells to tissue anatomy. Functional interrogation of TGFβ-, IL-7-, and IL-15-derived signals reveal subset-specific prostate TRM cell dependencies according to their niche-dependent phenotypes and distinct cytokine sources. For instance, TRM-promoting cytokines IL-15 and TGFβ are highest in the prostate epithelium where CD8+ T cells are most enriched for TRM-associated gene expression and analysis of human prostate samples identified similar patterns of both cytokine and CD8+ T cell localization. Thus, we provide a spatial framework of heterogenous T cell residence in the prostate, charting discrete tissue regions that influence T cell-fate through dynamic regulation of localized signals.