Lin Dajia, Zhong Shishun, Liu Jinsheng
Shengli Clinical Medical College of Fujian Medical University, Department of Gastrointestinal Surgery of Fujian Provincial Hospital, N0. 134, East Avenue, Fuzhou 350001, Fujian Province, China.
Shengli Clinical Medical College of Fujian Medical University, Department of Digestive Endoscopy of Fujian Provincial Hospital, N0. 134, East Avenue, Fuzhou 350001, Fujian Province, China.
Med Hypotheses. 2021 Jan;146:110358. doi: 10.1016/j.mehy.2020.110358. Epub 2020 Nov 10.
Mucosal associated invariant T (MAIT) cells have captured the attention of immunologists and clinicians in recent years due to their abundance in humans, especially in human liver and mucosal tissue. Colorectal cancer is one of the most common forms of cancer in mucosal tissue. Recent evidence reveal activated MAIT cells within the microenvironment of colorectal tumors. The increased tumor infiltration with MAIT cells correlates with poor survival in the colorectal cancer patients, suggesting MAIT cells are promising immunotherapeutic targets in colorectal cancer. Besides well-known role in anti-microbial immunity, MAIT cells have been associated with various forms of cancer. The Th1-biased MAIT cells are proposed to mediate anti-tumor immunity, while IL-17-producing subsets have been implicated in promoting malignancy. Reduced IFN-γ production and elevated IL-17 production of MAIT cells have been found in colorectal tumor tissue and shown to promote tumor growth and metastases. Although the mechanism(s) driving the increase in Th17-biased MAIT cells with reduced IFN-γ production in tumor is not fully understood, recent studies have linked IL-17 response to dysfunctional mitochondria and reactive oxygen species (ROS) from the mitochondria. Therefore, we hypothesize that mitochondrial dysfunction contributes to Th17-skewed MAIT cell responses with decreased IFN-γ production. Mitochondrial targeted antioxidants are supposed to be beneficial for recovering Th1-baised antitumor immunity and inhibiting IL-17 production of MAIT by improving mitochondrial function.
近年来，黏膜相关恒定T（MAIT）细胞因其在人类尤其是肝脏和黏膜组织中数量丰富，而吸引了免疫学家和临床医生的关注。结直肠癌是黏膜组织中最常见的癌症形式之一。最近的证据显示，在结直肠癌肿瘤微环境中存在活化的MAIT细胞。MAIT细胞在肿瘤组织中的浸润增加与结直肠癌患者的生存率低相关，这表明MAIT细胞是结直肠癌中有前景的免疫治疗靶点。除了在抗微生物免疫中的知名作用外，MAIT细胞还与多种癌症相关。偏向Th1的MAIT细胞被认为介导抗肿瘤免疫，而产生IL-17的亚群则与促进恶性肿瘤有关。在结直肠癌肿瘤组织中发现MAIT细胞的IFN-γ产生减少而IL-17产生增加，这促进了肿瘤生长和转移。尽管驱动肿瘤中偏向Th17的MAIT细胞增加且IFN-γ产生减少的机制尚未完全了解，但最近的研究已将IL-17反应与线粒体功能障碍和线粒体产生的活性氧（ROS）联系起来。因此，我们假设线粒体功能障碍导致了偏向Th17的MAIT细胞反应以及IFN-γ产生减少。线粒体靶向抗氧化剂应该有助于通过改善线粒体功能来恢复偏向Th1的抗肿瘤免疫并抑制MAIT细胞产生IL-17。
