Multifaceted functions of tissue-resident memory T cells in tumorigenesis and cancer immunotherapy

Tissue-resident memory T (T_RM) cells are well reported as a strong protective first line of defense against foreign antigens in non-lymphoid tissues. Moreover, T_RM cells have demonstrated critical protective roles in antitumor immunity, contributing to enhanced survival and tumor growth inhibition across various cancer types. However, surprisingly, recent studies suggest that T_RM cells can exhibit paradoxical effects, potentially promoting tumor progression under certain conditions and leading to adverse outcomes during antitumor immune responses. Understanding the complexities of T_RM cell functions will enable us to harness their potential in advancing cancer immunotherapy more effectively. Therefore, this review comprehensively investigates the dual roles of T_RM cells in different tumor contexts, highlighting their protective functions in combating cancers and their unfavorable potential to exacerbate tumor development. Additionally, we explore the implications of T_RM cell behaviors for future cancer treatment strategies, emphasizing the need for further research to optimize the therapeutic exploitation of T_RM cells while mitigating their deleterious effects.