The Emerging Role of Tissue-Resident Memory CD8+ T Lymphocytes in Human Digestive Tract Cancers

Abstract

Malignant digestive tract tumors are a great threat to human public health. In addition to surgery, immunotherapy brings hope for the treatment of these tumors. Tissue-resident memory CD8+ T (Trm) cells are a focus of tumor immunology research and treatment due to their powerful cytotoxic effects, ability to directly kill epithelial-derived tumor cells, and overall impact on maintaining mucosal homeostasis and antitumor function in the digestive tract. They are a group of noncirculating immune cells expressing adhesion and migration molecules such as CD69, CD103, and CD49a that primarily reside on the barrier epithelium of nonlymphoid organs and respond rapidly to both viral and bacterial infection and tumorigenesis. This review highlights new research exploring the role of CD8+ Trm cells in a variety of digestive tract malignant tumors, including esophageal cancer, gastric cancer, colorectal cancer, and hepatocellular carcinoma. A summary of CD8+ Trm cell phenotypes and characteristics, tissue distribution, and antitumor functions in different tumor environments is provided, illustrating how these cells may be used in immunotherapies against digestive tract tumors.

Cytolytic CD4+ and CD8+ Regulatory T-Cells and Implications for Developing Immunotherapies to Combat Graft-Versus-Host Disease

“…While these reports do indicate that some CD8 + CD103 + Treg may have both suppressive and cytolytic potential, the current the literature is still unable to phenotypically distinguish between the immunosuppressive, cytolytic and dual function populations. A possible explanation to these varying mechanisms used by CD8 + CD103 + Treg is that CD103 expression is likely not a conserved marker of CD8 + Treg, as several studies have also reported CD103 expression as a marker of activated tissue-resident memory T-cells (Trm) ( 196 , 197 ). In fact, CD8 + CD103 + Trm cells have been shown to be significant contributors to anti-tumor immunity due to their substantial cytotoxicity and cytokine production potential ( 196 – 199 ).…”

“…A possible explanation to these varying mechanisms used by CD8 + CD103 + Treg is that CD103 expression is likely not a conserved marker of CD8 + Treg, as several studies have also reported CD103 expression as a marker of activated tissue-resident memory T-cells (Trm) ( 196 , 197 ). In fact, CD8 + CD103 + Trm cells have been shown to be significant contributors to anti-tumor immunity due to their substantial cytotoxicity and cytokine production potential ( 196 – 199 ). Despite this, CD8 + CD103 + cyTreg are an increasingly interesting Treg population that necessitates further investigation.…”

Folate Receptor 4-Expressing T cell Is Associated with Disease-Free Survival in Patients with Esophageal Squamous Cell Carcinoma

“…The survival time of patients with high FR4 expression was significantly prolonged after adjuvant chemotherapy. Patients' immune status affects the response to comprehensive therapy, and the proportion of T cell subsets and tumor-associated macrophages can predict the efficacy of comprehensive therapy for esophageal cancer [ 10 ]. Regulatory T cells in tumors are mostly marked by Foxp3.…”

“…The H -score was calculated using the following formula: (3 × percentage of cells with strong staining) + (2 × percentage of cell with moderate staining) + (1 × percentage of cells with weak staining). IL-22 expression was classified into two groups according to a cutoff H -score of 100 [ 10 ]. For CD4 (clone BM4263, 1 : 50 dilution, Boster, Wuhan, China), CD8 (clone BM4379, 1 : 30 dilution, Boster, Wuhan, China), FOXP3 (clone ab20034, 1 : 50 dilution, Abcam, Cambridge, UK), and CD68 (clone BA3639, 1 : 100 dilution, Boster, Wuhan, China) immunohistochemistry staining, expression in nuclei of lymphocytes was defined as positive.…”

Current and Future Biomarkers for Immune Checkpoint Inhibitors in Head and Neck Squamous Cell Carcinoma

“…In human cancers, tumor-infiltration Trm cells have been found to promote anti-tumor immunity and are associated with improved survival in HNSCC [ 71 , 72 ]. Trm cells in tumors are highly enriched with immune checkpoints including PD-L1 and LAG3 and are expanded significantly early with ICI therapy and the levels of CD8+CD103+ T RM are associated with improved patient survival suggesting a critical role Trm in ICI-mediated immune response and its potential predictive value [ 71 , 73 ]. In addition to tumor-infiltrating immune cell composition, the expression of specific immune-related genes in TME has been shown to correlate with clinical outcomes with ICIs in the HNSCC population.…”