Holding our breath: The promise of tissue-resident memory T cells in lung cancer

T cell memory is critical in controlling infection and plays an important role in anti-tumor responses in solid cancers. While effector memory and central memory T cells circulate and patrol non-lymphoid and lymphoid organs respectively, tissue resident memory T cells (T_RM) permanently reside in tissues and provide local protective immune responses. In a number of solid tumors, tumor-specific T cell memory responses likely play an important role in keeping tumors in check, limiting cancer cell dissemination and reducing risk of relapse. In non-small cell lung cancer (NSCLC), a subset of tumor infiltrating lymphocytes (TILs) display phenotypic and functional characteristics associated with lung T_RM (T_RM-like TILs), including the expression of tissue-specific homing molecules and immune exhaustion markers. High infiltration of T_RM-like TILs correlates with better survival outcomes for lung cancer patients, indicating that T_RM-like TILs may contribute to anti-tumor responses. However, a number of T_RM-like TILs do not display tumor specificity and the exact role of T_RM-like TILs in mediating anti-tumor response in lung cancer is unclear. Here we review the characteristics of T_RM-like TILs in lung cancer, the role these cells play in mediating anti-tumor immunity and the therapeutic implications of T_RM-like TILs in the use and development of immunotherapy for lung cancer.