Circulating and tumor-infiltrating mucosal associated invariant T (MAIT) cells in colorectal cancer patients

Abstract

Mucosal associated invariant T (MAIT) cells are important for immune defense against infectiousMucosal associated invariant T (MAIT) cells are innate-like T cells expressing a semi-invariant T cell receptor (TCR) of Vα 7.2-Jα 33 chain and a limited array of Vβ 2 or Vβ 13 chain in humans 1 . Circulating and tissue-infiltrating MAIT cells can be characterized by expressing Vα 7.2 segment with either CD161 or IL-18Rα on cell surface 2,3 . MAIT cells are preferably resident in the intestinal mucosa and liver in humans [4][5][6] . In contrast to conventional T cells that recognize specific antigen peptides, MAIT cells can recognize and respond to microbial vitamin B metabolites in the major histocompatibility complex class I (MHC I)-related molecule (MR1) restricted manner [7][8][9][10] . Co-cultured with bacterium-infected antigen presenting cells (APC), activated MAIT cells can produce diverse cytokines, including interferon-γ (IFN-γ ), tumor necrosis factor-α (TNF-α ) and interleukin-17A (IL-17A) 3,11,12 .It was considered that MAIT cells acquired memory phenotypes after birth and accumulated in the lamina propria of intestinal mucosa in a manner depending on B cells and the commensal flora 13 . However, a recent study in the human fetus indicates that MAIT cells can acquire memory phenotypes before birth, independent of established commensal flora 14 . Previous studies have shown the importance of MAIT cells in host defense against various infectious pathogens 15-18 . Notably, accumulative MAIT cells protect from TNBS-induced colitis in rodents 19 and inflammatory bowel disease in humans 20 . Therefore, MAIT cells in the intestinal lamina propria may be natural protectors from infection and inflammation.Colorectal cancer (CRC) is one of the most common malignant tumors worldwide. The pathogenesis of CRC is attributed to epithelial genetic mutations, impaired mucosal integrity, disordered microbiota and inflammation 21 . CRC usually disrupts the mucosal homeostasis and barrier function. Its development and progression

Clinical relevance of circulating mucosal-associated invariant T cell levels and their anti-cancer activity in patients with mucosal-associated cancer

“…In the present study, MAIT cells were found to be more accumulated in colon cancer tissue than in the unaffected tissue, consistent with previous studies [14, 34]. Circulating MAIT cells have been reported to preferentially express CCR6, supporting their migration to the intestine [9].…”

Functional impairment of infiltrating T cells in human colorectal cancer

“…While higher frequencies of IL-17-producing cells have been reported in colorectal tumors, [9][10][11][12]14 to our knowledge this is the first time that enhanced cytokine production per cell by inflammatory T cells infiltrating the CRC TME has been reported. The TME has high levels of cytokines that boost inflammatory T cell differentiation and function such as IL-6.…”

“…We and others have shown a higher frequency of IL-17-producing T cell populations, including MAIT cells and gd T cells, in tumor versus adjacent bowel tissue. [9][10][11][12][13][14] Differences in the frequency of regulatory T cells (Tregs) have also been observed, 10,11 but the effect of the function of these T cell populations on other infiltrating T cells is not clear. We hypothesized that T cells in tumor tissue would have impaired cytokine production and proliferative ability due to the suppressive environment in CRC tumors.…”

MDR1 in immunity: friend or foe?

“…A recent study, conducted on advanced human colorectal cancer (CRC) tissues showed, a significant higher frequency of MDR1 + CD161 + T cells, considered mostly as MAIT cells by the authors, in the tumor tissue compared to adjacent healthy tissues. 100 In this matter, evaluation of MDR1 expression by immune subtypes should be more extensively investigated. The hostile tumor micro-environment and its chemical composition must indeed shape the immune infiltrate, and MDR1 expression by anti-tumor immune cells may favor their preservation despite harsh environmental conditions.…”