Dataset Information

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 infectious pathogens and regulate the pathogenesis of various inflammatory diseases. However, their roles in the development of colorectal cancer (CRC) are still unclear. This study examined the phenotype, distribution, clinical relevance and potential function of MAIT cells in CRC patients. We found that the percentages of circulating memory CD8(+) MAIT cells were significantly reduced while tumor infiltrating MAIT cells were increased, especially in patients with advanced CRC. The serum CEA levels were positively correlated with the percentages of tumor infiltrating MAIT cells in CRC patients, but negatively correlated with the percentages of circulating MAIT in advanced CRC patients. Activated circulating MAIT cells from CRC patients produced lower IFN-?, but higher IL-17. Furthermore, higher levels of V?7.2-J?33, IFN-? and IL-17A were expressed in the CRC tissues. Co-culture of activated MAIT cells with HCT116 cells enhanced IL-17 expression and induced HCT116 cell cycle arrest at G2/M phase in a contact- and dose-dependent manner, which was abrogated by treatment with anti-MR1. Therefore, MAIT cells preferably infiltrate into the solid tumor in CRC patients and may participate in the immune surveillance of CRC.

SUBMITTER: Ling L

PROVIDER: S-EPMC4738248 | biostudies-other | 2016 Feb

REPOSITORIES: biostudies-other

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

Ling Limian L Lin Yuyang Y Zheng Wenwen W Hong Sen S Tang Xiuqi X Zhao Pingwei P Li Ming M Ni Jingsong J Li Chenguang C Wang Lei L Jiang Yanfang Y

Scientific reports 20160203

Mucosal associated invariant T (MAIT) cells are important for immune defense against infectious pathogens and regulate the pathogenesis of various inflammatory diseases. However, their roles in the development of colorectal cancer (CRC) are still unclear. This study examined the phenotype, distribution, clinical relevance and potential function of MAIT cells in CRC patients. We found that the percentages of circulating memory CD8(+) MAIT cells were significantly reduced while tumor infiltrating ...[more]

PMID: 26837580

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Project description:T-cell exhaustion represents a progressive loss of T-cell function. The inhibitory receptor PD-1 is known to negatively regulate CD8+ T cell responses directed against tumor antigen, but the blockades of PD-1 pathway didn't show the objective responses in patients with colorectal cancer (CRC). Thus, further exploring the molecular mechanism responsible for inducing T-cell dysfunction in CRC patients may reveal effective strategies for immune therapy. This study aims to characterize co-inhibitory receptors on T cells in CRC patients to identify novel targets for immunotherapy. In this study, peripheral blood samples from 20 healthy controls and 54 consented CRC patients, and tumor and matched paraneoplastic tissues from 7 patients with advanced CRC, subjected to multicolor flow cytometric analysis of the expression of PD-1 and Tim-3 receptors on CD8+ T cells. It was found that CRC patients presented with significantly higher levels of circulating Tim-3+PD-1+CD8+ T cells compared to the healthy controls (medians of 3.12% and 1.99%, respectively, p = 0.0403). A similar increase of Tim-3+PD-1+CD8+ T cells was also observed in the tumor tissues compared to paraneoplastic tussues. Tim-3+PD-1+CD8+ T cells in tumor tissues produced even less cytokine than that in paraneoplastic tissues. Functional ex vivo experiments showed that Tim-3+PD-1+CD8+ T cells produced significantly less IFN-? than Tim-3-PD-1-CD8+ T cells, followed by Tim-3+PD-1-CD8+ T cells, and Tim-3-PD-1+CD8+ T cells, indicating a stronger inhibition of IFN-? production of Tim-3+CD8+ T cells . It is also found in this study that Tim-3+PD-1+CD8+ T cell increase in circulation was correlated with clinical cancer stage but not histologic grade and serum concentrations of cancer biomarker CEA. Our results indicate that upregulation of the inhibitory receptor Tim-3 may restrict T cell responses in CRC patients, and therefore blockage of Tim-3 and thus restoring T cell responses may be a potential therapeutic approach for CRC patients.

Dataset Information

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

Publications

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

Similar Datasets

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