Tissue-Resident Memory T Cells: Pioneering New Avenues in Cancer Immunotherapy

Tissue-resident memory T cells (T_RM) are a specialized subset of memory T cells that reside in nonlymphoid tissues and draining lymph nodes, playing a critical role in immune surveillance and tumor immunity. Tumor-infiltrated T_RM have emerged as key players in immune checkpoint blockade (ICB) therapy, contributing to early therapeutic responses and tumor control.

This review aims to comprehensively summarize the identification, functional roles, and regulatory mechanisms of T_RM in the context of tumor immunity, and to explore innovative strategies for enhancing T_RM-mediated anti-tumor responses.

We reviewed recent literature on T_RM biology, focusing on their transcriptional regulation, phenotypic characteristics, and interactions within the tumor microenvironment. We also reviewed current strategies for modulating T_RM function to improve cancer immunotherapy outcomes.

T_RM can remodel the tumor microenvironment, suppress tumor progression, and enhance ICB efficacy. Their function is tightly regulated by transcription factors and phenotypic molecules. Targeted manipulation of these regulatory mechanisms has shown potential in enhancing T_RM/T_RM-like cell activity and overcoming resistance to ICB therapy.

T_RM represent a promising target for cancer immunotherapy due to their potent anti-tumor functions and responsiveness to ICB. Understanding their biology and regulatory networks opens new avenues for therapeutic intervention.