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

Abstract

Background: Tissue-resident memory T cells (TRM) 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 TRM have emerged as key players in immune checkpoint blockade (ICB) therapy, contributing to early therapeutic responses and tumor control. Aims: This review aims to comprehensively summarize the identification, functional roles, and regulatory mechanisms of TRM in the context of tumor immunity, and to explore innovative strategies for enhancing TRM-mediated anti-tumor responses. Methods: We reviewed recent literature on TRM biology, focusing on their transcriptional regulation, phenotypic characteristics, and interactions within the tumor microenvironment. We also reviewed current strategies for modulating TRM function to improve cancer immunotherapy outcomes. Results: TRM 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 TRM/TRM-like cell activity and overcoming resistance to ICB therapy. Conclusion: TRM 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.