Fig. 2. CD8 + TRMs in cancer.

TRMs expressing CD103 and CD69 have been identified in numerous cancerous tissues. The presence of TRMs within and around tumor tissues are often associated with improved patient outcomes. Their favorable positioning within the tissues makes TRMs rapid first-line effectors that may suppress and eliminate local tumor growths. In an MHC-I dependent fashion, TRMs can directly lyse tumor cells via release of cytotoxic molecules, such as granzyme B and perforin. Alternatively, TRMs may also influence the local tumor microenvironment (TME) through their enhanced expression of inflammatory cytokines i.e., IFNγ, TNF and IL-2. Expression of inhibitory receptors such as PD-1, CTLA-4, LAG-3, TIM-3 and TIGIT have also found to be elevated on TRMs making them attractive targets for checkpoint blockade therapies. Indeed, tumor-specific TRMs targeted by anti-PD-1 show enhanced reactivity toward autologous tumor samples. Local signals within the TME such as TGF-b or VCAM-1 signaling may also shape TRMs phenotype and survival by influencing TRM markers such as CD103, thus improving retention within tumor tissues.