Kennidy K. Takehara, Alexander Monell, Vida Luna, Baxter Melisso, K Mempel, Kitty P. Cheung, Natalie Zane, Peter P. Challita, Amir Ferry, Ethan C. Xu, Violante Olivari, Nicole E. Scharping, Giovanni Galletti, Sara Quon, J Ishibashi, Nina Estep, John B. Johanneson, Chinmayi Pandya, Stephanie Añover-Sombke, Rana R. McKay, Peter J. Skene, Matthew E. Pipkin, Maximilian Heeg, Miguel Reina-Campos, Ananda W. Goldrath
The prostate is an important exocrine organ, a barrier tissue of the male reproductive system, and a common site of malignancy, yet CD8 + T cells in the prostate 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, combined with functional interrogation of 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 the discrete tissue regions that influence T cell fate through dynamic regulation of localized signals.