Mo Juanfen, Zheng Li, Gao Zhenzhen, Wu Jiayuan, Bao Yi
The Key Laboratory, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, 314000, People's Republic of China.
Department of Oncology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, 314000, People's Republic of China.
Onco Targets Ther. 2021 Nov 16;14:5263-5273. doi: 10.2147/OTT.S332822. eCollection 2021.
Mucosal-associated invariant T (MAIT) cells are a group of unconventional T cells, which strongly express CD161 and are involved in defending against infectious pathogens and inflammatory diseases. They are activated by inflammatory cytokines, secrete various cytokines and cytotoxic molecules, and express chemokine receptors and integrins. However, the underlying mechanisms of MAIT cells in colon cancer are still not fully understood.
The phenotype and frequency of circulating MAIT cells were investigated by flow cytometry in colon cancer patients and healthy donors. CD161 was examined in cancerous and paracancerous nontumor tissues of colon cancer patients by immunohistochemistry. The serum levels of IFN-γ and IL-17A were analyzed by ELISA. Finally, MAIT cells were also detected in peripheral blood and tumor tissues in a CT26 tumor-bearing mice model.
The percentages of CD4CD8 MAIT cells, CD4CD8 MAIT cells, and CD4CD8 MAIT cells increased in the peripheral blood of colon cancer patients compared with healthy donors. The expression of CD161 protein in colon cancer cancerous tissues was higher than that in the paracancerous nontumor tissues. The killer cell lectin-like receptor B1 (KLRB1), a coding gene for CD161, was positively associated with the gene expressions of immune inhibitory receptors, such as CTLA4, HAVCR2, PDCD1, and CD274 in colon cancer. Furthermore, the serum levels of IFN-γ and CEA were positively correlated with CD8 MAIT cells in the peripheral blood of colon cancer patients.
Taken together, our data suggest that the circulating MAIT cells and the expression of CD161 protein in the tumor tissues increased in colon cancer patients, and MAIT cells may participate immune activities in colon cancer.
黏膜相关恒定T（MAIT）细胞是一群非常规T细胞，它们强烈表达CD161，参与抵御感染性病原体和炎症性疾病。它们被炎性细胞因子激活，分泌多种细胞因子和细胞毒性分子，并表达趋化因子受体和整合素。然而，MAIT细胞在结肠癌中的潜在机制仍未完全阐明。
通过流式细胞术研究结肠癌患者和健康供体循环MAIT细胞的表型和频率。采用免疫组织化学法检测结肠癌患者癌组织和癌旁非肿瘤组织中的CD161。通过酶联免疫吸附测定法分析血清中干扰素-γ（IFN-γ）和白细胞介素-17A（IL-17A）水平。最后，在CT26荷瘤小鼠模型的外周血和肿瘤组织中也检测了MAIT细胞。
与健康供体相比，结肠癌患者外周血中CD4⁺CD8⁻ MAIT细胞、CD4⁻CD8⁺ MAIT细胞和CD4⁻CD8⁻ MAIT细胞的百分比增加。结肠癌癌组织中CD161蛋白的表达高于癌旁非肿瘤组织。CD161的编码基因杀伤细胞凝集素样受体B1（KLRB1）与结肠癌中免疫抑制受体如细胞毒性T淋巴细胞相关抗原4（CTLA4）、甲型肝炎病毒细胞受体2（HAVCR2）、程序性死亡蛋白1（PDCD1）和程序性死亡配体1（CD274）的基因表达呈正相关。此外，结肠癌患者外周血中IFN-γ和癌胚抗原（CEA）的血清水平与CD8⁺ MAIT细胞呈正相关。
综上所述，我们的数据表明，结肠癌患者循环MAIT细胞及肿瘤组织中CD161蛋白表达增加，MAIT细胞可能参与结肠癌的免疫活动。
