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肿瘤代谢与营养电子杂志
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益生菌调控肠道菌群对免疫检查点阻断治疗的影响
免疫检查点阻断是一种肿瘤免疫治疗的突破性技术。利用单克隆抗体抑制机体靶向的负调控信号,激活下游免疫反 应,能够产生由细胞毒性T细胞介导的杀伤肿瘤细胞的作用。然而这种疗法只能令少数患者受益,因此研究并开发提高免疫疗 效的方法具有重要意义。肠道菌群被认为对肿瘤免疫检查点阻断治疗的成功有重要的贡献。研究表明,肠道菌群的存在、组成 和多样性水平直接影响患者和小鼠的肿瘤治疗效果,并且免疫应答效率能通过粪菌移植或有益菌干预而改善。肠道的特征菌群 与宿主肿瘤微环境树突状细胞的抗原呈递功能和效应性T淋巴细胞的活性有显著的相关性。这种菌群‐免疫之间的调控机制很 大程度上是由肠道菌群代谢产生的短链脂肪酸或次级胆汁酸等物质通过配体‐受体的关系调控宿主基因表达,调节免疫细胞分 化及活性。另外,肠道细菌还可能通过易位定植于肿瘤组织进而刺激免疫反应。基于这些菌群与免疫关系的研究,可确信通过 避免使用抗生素、粪菌移植和益生菌干预的方法,改善或维持健康的肠道菌群结构,是优化肿瘤免疫检查点阻断治疗的有效途径。
内蒙古农业大学乳品生物技术与工程教育部重点实验室, 呼和浩特 010018
Influence of probiotic‑regulated gut microbiota on immune checkpoint blockade therapy
Immune checkpoint blockade is a breakthrough technology in tumor immunotherapy. It could be summarized that monoclonal antibodies suppressed the target negative regulators to activate the downstream immune response, which produced a cytotoxic T cell mediated killing effect on tumor cells. However, this treatment can only benefit a part of patients, so it is important to find out effective ways to improve the cancer immunotherapy. Gut microbiota is considered to be an important contribution to the success of checkpoint blockade therapy. Studies showed that the presence, composition, and diversity of gut microbiota directly affected the efficacy of cancer treatment in patients and mice, and the efficiency of the immune response could be improved by fecal microbiota transplantation or beneficial bacteria intervention. There was a significant correlation between the characteristic bacteria or microbiota of intestinal tract and the antigen presentation of dendritic cells in the host tumor microenvironment as well as the activity of effector T lymphocytes. To a large extent, the regulation mechanism between gut microbiota and host immunity is that substances, such as short?chain fatty acids or secondary bile acids, produced by gut bacteria metabolism can regulate the gene expression or the differentiation and activity of immune cells through ligand?receptor pathways. Another possible factor can be supposed as that bacterial translocation into the tumor stimulates the systemic immune response. Based on these gut microbiota?host immune investigations, it can be confirmed that improving or maintaining healthy intestinal microbiota structure by avoiding the use of antibiotics, fecal bacteria transplantation or probiotic intervention is an effective way to optimize the immune checkpoint blockade treatment of tumor.
Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot 010018, Inner Mongolia, China