Resident Memory T Cells in the Tumor Microenvironment

Tissue-resident memory T (T_RM) cells are strategically positioned within the epithelial layers of many tissues to provide enduring site-specific immunological memory. This unique T-cell lineage is endowed with the capacity to rapidly respond to tissue perturbations and has a well-documented role in eradicating pathogens upon reexposure. Emerging evidence has highlighted a key role for T_RM cells in cancer immunity. Single-cell approaches have identified T_RM cells among other CD8⁺ tumor-infiltrating lymphocyte (TIL) subsets, and their presence is a positive indicator of clinical outcome in cancer patients. Furthermore, recent preclinical studies have elegantly demonstrated that T_RM cells are a critical component of the antitumor immune response. Given their unique functional abilities, T_RM cells have emerged as a potential immunotherapeutic target. Here, we discuss T_RM cells in the framework of the cancer-immunity cycle and in the context of the T cell- and non-T cell-inflamed tumor microenvironments (TME). We highlight how their core features make T_RM cells uniquely suited to function within the metabolically demanding TME. Finally, we consider potential therapeutic avenues that target T_RM cells to augment the antitumor immune response.