Resident Memory T Cells and Their Effect on Cancer

Abstract

Resident memory T (T_RM) cells are a unique subset of CD8⁺ T cells that are present within certain tissues and do not recirculate through the blood. Long term memory establishment and maintenance are dependent on tissue population of memory T cells. They are characterized by dual CD69/CD103 positivity, and play a role in both response to viral infection and local cancer immunosurveillance. Human T_RM cells demonstrate the increased expression of adhesion molecules to facilitate tissue retention, have reduced proliferation and produce both regulatory and immune responsive cytokines. T_RM cell phenotype is often characterized by a distinct expression profile driven by Runx3, Blimp1, and Hobit transcription factors. The accumulation of T_RM cells in tumors is associated with increased survival and response to immunotherapies, including anti-PD-1 and anti-CTLA-4. In this review, we explore potential mechanisms of T_RM cell transformation and maintenance, as well as potential applications for the use of T_RM cells in both the development of supportive therapies and establishing more accurate prognoses.

Keywords: cancer vaccine; immunotherapy; memory T cells.

Figure 1

CD8⁺ T cells enter tissues and are stimulated by TGF-ß, IL-33, and IL-15 to upregulate the tissue-retention surface markers, CD69 and CD103, while simultaneously down-regulating the tissue-egress markers, CD62L and CCR7. This creates a resident memory T (T_RM) cell phenotype, enabling T_RM cells to maintain close contact with malignant cells residing within tissues.