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Tissue-resident memory CD8+ T cell (TRM) is a specialized memory T lymphocyte that is retained long-term within non-lymphoid peripheral tissues, independent of circulation. TRM cells express markers (CD69, CD103, CD49a) promoting local retention and barrier tissue residency, and are capable of immediate effector function upon secondary antigen encounter. They occupy tissue niches—skin, mucosa, lungs, gut—where they patrol and respond to infections and malignant transformation, playing a decisive role in protective immunity and clinical outcomes in cancer and infection. Their unique biology includes distinct epigenetic programming and differentiation pathways, making them promising targets for both vaccination (to boost local immunity) and cancer therapies (to enhance tumor immune infiltration). However, their activation can also contribute to autoimmunity and chronic inflammatory conditions, presenting therapeutic challenges[2][1][4][6][9][3][7][8][5][10].
Immune checkpoint inhibition: By targeting PD-1/PD-L1 pathways, drugs unleash cytotoxic functions of CD8+ TRM cells within tumors, augmenting local antitumor immunity. Vaccination: Strategies induce TRM differentiation and retention at barrier sites, enhancing rapid tissue-specific protection.
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