Tissue-Resident Memory T Cells in Cancer Immunosurveillance

TRM cells are non-recirculating immune cells that reside in peripheral tissues where they can protect against local infections and cancer. CD69+CD103+ TRM-like cells accumulate in various human solid cancers where they have been associated with improved disease outcomes and patient survival. Vaccine-generated TRM cells can protect against tumor challenge independently of TCIRC cells. TRM cells may mediate tumor protection by promoting tumor-immune equilibrium through the secretion of cytokines and/or via CD103-enhanced tumor cell killing. TRM cells express inhibitory checkpoint molecules and may serve as potential targets for cancer immunotherapy. Following their activation and expansion in response to foreign threats, many T cells are retained in peripheral tissues without recirculating in the blood. These tissue-resident CD8+ memory T (TRM) cells patrol barrier surfaces and nonlymphoid organs, where their critical role in protecting against viral and bacterial infections is well established. Recent evidence suggests that TRM cells also play a vital part in preventing the development and spread of solid tumors. Here, we discuss the emerging role of TRM cells in anticancer immunity. We highlight defining features of tumor-localizing TRM cells, examine the mechanisms through which they have recently been shown to suppress cancer growth, and explore their potential as future targets of cancer immunotherapy. Following their activation and expansion in response to foreign threats, many T cells are retained in peripheral tissues without recirculating in the blood. These tissue-resident CD8+ memory T (TRM) cells patrol barrier surfaces and nonlymphoid organs, where their critical role in protecting against viral and bacterial infections is well established. Recent evidence suggests that TRM cells also play a vital part in preventing the development and spread of solid tumors. Here, we discuss the emerging role of TRM cells in anticancer immunity. We highlight defining features of tumor-localizing TRM cells, examine the mechanisms through which they have recently been shown to suppress cancer growth, and explore their potential as future targets of cancer immunotherapy. transfer of preactivated and/or tumor-specific immune cells into a patient to treat cancer. ectonucleoside triphosphate diphosphohydrolase-1 (ENTPD1); cell-surface molecule that hydrolyzes extracellular ATP; usually marks activated or exhausted T cells. subset of memory T cells that migrate through blood and secondary lymphoid organs; characterized by heightened expression of L-selectin (CD62L) and CCR7. T cell engineered to express a modified T cell receptor (TCR) specific for a protein expressed by cancer cells that differs from that recognized by their endogenous TCR. memory T cells that continuously migrate through blood and secondary lymphoid organs; includes both effector and central memory T cell subsets. subset of memory T cells that migrate through peripheral tissues and the blood; characterized by low expression of both CD62L and CCR7. process through which immune cells completely kill and eradicate cancerous cells. process during which epithelial or cancerous cells lose cell–cell adhesion properties and acquire heightened invasive and metastatic potential. process through which immune cells suppress cancer growth without completely removing tumor cells from the body. state of T cell dysfunction characterized by a loss of effector function resulting from unrelenting antigen stimulation and/or chronic infection. sphingosine 1-phosphate receptor antagonist that enforces lymphocyte retention within lymphoid organs by blocking their egress. DNA-binding transcription factor encoded by the Znf638 gene; a master regulator of tissue residency in both innate and adaptive lymphocytes. drug treatments (usually antibody therapies, e.g., anti-PD-1, anti-PD-L1, anti-CTLA-4) designed to activate or enhance anticancer immune responses. evolutionary process comprising elimination, equilibrium, and escape phases through which immune cells select for less immunogenic tumor cell clones that arise during tumor progression. point of contact between a lymphocyte and an antigen-presenting or target cell. newly generated tumor-specific antigen that arises through mutations occurring during cancer growth. experimental process during which the circulatory systems of two animals are joined to investigate migratory properties of immune cells. cell-surface immune checkpoint molecule encoded by the Pdcd1 gene that negatively regulates T cell activation and function. DNA-binding transcription factor encoded by the Tcf7 gene, involved in T cell differentiation and expressed by proliferative or stem-like subsets of tumor-infiltrating T cells. cell-surface immune checkpoint molecule encoded by the Havcr2 gene and associated with T cell dysfunction. T helper 1; CD4+ T cells or immune response involving effector molecules canonically tailored to combat intracellular pathogens or cancerous cells, including IFN-γ and TNF. T helper 2; CD4+ T cells or immune response involving effector molecules canonically tailored to combat parasites; may be associated with allergy, including IL-4, IL-5, and IL-13. T helper 17; CD4+ T cells or immune response involving effector molecules canonically tailored to combat extracellular bacteria and that may be associated with autoimmune diseases, including IL-17. subset of memory T cells that reside permanently within peripheral or nonlymphoid tissues, without recirculating in blood. space and factors within and surrounding cancer cells, including stromal and immune cells that infiltrate a tumor and the molecules they produce. cell-surface molecule that binds collagen IV and may be involved in T cell migration, cell adhesion, and cytotoxic activity. autoimmune disease in which immune cells target and kill melanocytes, leading to depigmentation of the skin.