T-cell immunoglobulin and ITIM domain, as a potential immune checkpoint target for immunotherapy of colorectal cancer

Abstract

The importance of the tumor microenvironment in cancer progression has been well studied for many years. Immune checkpoint inhibitors (ICIs) are regarded as potential strategies in enhancing the immune responses in patients with cancer, particularly colorectal cancer (CRC). Notably, CRCs are extraordinarily heterogeneous and mostly are microsatellite-stable (MSS) or cold tumors, which means that the immune response is not usually as strong as that of foreign cells. T-cell immunoglobulin and ITIM domain (TIGIT) is a new immune checkpoint receptor overexpressed inside the CRC tumor-immune microenvironments. Moreover, several studies have shown that TIGIT in combination with other ICIs and/or conventional treatments, can lead to a robust anti-tumor response in CRC. This review looks deep inside TIGIT expression patterns, their various functions, and possible immunotherapy strategies to increase survival rates and decrease immune-related adverse events.

Keywords: AML acute myelogenous leukemia; APCs antigen-presenting cells; CAFs cancer-associated fibroblasts; CRC colorectal cancer; DC Dendritic Cells; DFS disease-free survival; EMT epithelial-mesenchymal transition; ETBF Bacteroides fragilis; F. nucleatum Fusobacterium nucleatum; Fgl2 fibrinogen-like protein 2; Grb2 growth factor receptor-bound protein 2; IBD inflammatory bowel diseases; ICIs Immune checkpoint inhibitors; IHC immunohistochemistry; List of Abbreviations and symbols:; MAPK mitogen-activated protein kinase; MDSCs myeloid-derived suppressor cells; MSI Microsatellite instability; MSS microsatellite-stable; NFκB nuclear factor-kappa B; NK Natural Killer cell; NSCLC non-small cell lung cancer; PI3K phosphoinositide 3-kinase; PVR poliovirus receptor; RR-MS relapsing-remitting multiple sclerosis; SHIP1 SH2 domain-containing inositol-5-phosphatase 1; TAMs tumor-associated macrophages; TANs tumor-associated neutrophils; TFH follicular helper T cells; TFR follicular regulatory T cells; TIGIT; TIGIT T cell immunoglobulin and ITIM domain; TILs tumor-infiltrating lymphocytes; TME tumor microenvironment; TNM staging spread of cancer to other parts of the body; Tregs regulatory T cells; cancer immunotherapy; colorectal cancer; dMMR defective DNA mismatch repair; immune checkpoint; mAb monoclonal antibody.