Tissue-resident memory T cells reshape in situ immune surveillance at luminal barriers and during early cancer...

Tissue-resident memory T (TRM) cells provide a conceptual framework for understanding how barrier tissues sense, restrict and amplify immune responses at the earliest sites of danger. Rather than viewing memory primarily through the delayed recruitment of recirculating cells, the TRM perspective places immune memory within defined tissue niches, where cellular position, antigen experience, egress restraint, metabolic adaptation and local cellular interactions collectively determine the quality of in situ surveillance. Here we outline the conceptual evolution and definitional boundaries of TRM cells, distinguish complementary CD4⁺ and CD8⁺ TRM programmes across luminal barriers, and place particular emphasis on TRM cells in tumour surveillance, immunotherapy response, precancerous niches and mammary duct interception. We also integrate recent human reproductive tract phenotyping data to link TRM states with clinically relevant tissue contexts. We argue that future TRM studies should move beyond CD69 or CD103-based annotation and instead build evidence chains that integrate multi-omics, spatial biology, TCR clonality and functional validation. The mammary duct is not a classical mucosal organ, but it may become a critical setting in which to test how far TRM-based principles of in situ immunity can be extended to cancer prevention and local immune intervention.