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肠道菌群影响肿瘤免疫治疗的机制及临床应用研究进展

  • 张雪莹 ,
  • 秦环龙
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  • 同济大学附属第十人民医院肠道微生态诊疗中心,上海 200072/同济大学医学院肠道疾病研究所,上海 200072

网络出版日期: 2021-04-12

基金资助

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Progress on the mechanism and clinical application of gut microbiota in tumor immunotherapy

  • Zhang Xueying ,
  • Qin Huanlong
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  • Intestinal Microenvironment Treatment Center, the Tenth People’s Hospital Affiliated to Tongji University, Shanghai 200072, China/Institute for Intestinal Diseases, Medical School of Tongji University, Shanghai 200072, China

Online published: 2021-04-12

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摘要

肿瘤免疫治疗是继手术、化疗、放疗后的第四种疗法,在部分上皮性肿瘤和血液性肿瘤的治疗中取得较大突破,但不良反应常见甚至比较严重,在部分实体肿瘤中的应答率也不够理想。随着基因组学和代谢组学技术的成熟,人们逐渐认识到肠道菌群在肿瘤发展与治疗中的作用。菌群可能通过调节宿主免疫系统和肿瘤微环境等方式影响肿瘤免疫,部分细菌通过激活免疫起到协助对抗肿瘤的作用,而有些细菌则介导免疫抑制帮助癌细胞逃避免疫系统的杀伤。越来越多的研究揭示肿瘤免疫治疗的效果和并发症与患者肠道菌群组成有关,对治疗敏感或易发生不良反应的患者肠道菌群组成有一定特征。这些特征可能作为生物标志物来预测免疫治疗的预后,也可能被开发为“免疫增效剂”(如Akk菌和双歧杆菌)来辅助免疫治疗。部分临床和临床前研究已证明包括菌群移植在内的微生物干预能一定程度上提高免疫治疗的敏感性或减轻不良反应。随着基因编辑技术和纳米技术的发展,有助于免疫治疗的工程细菌的设计开发成为了新的研究热点。基于肠道菌群和免疫治疗的关系,正确挖掘微生物信息、开发合理可行的微生物干预手段,有希望在很大程度上优化肿瘤免疫疗法,为肿瘤治疗带来新的突破。

本文引用格式

张雪莹 , 秦环龙 . 肠道菌群影响肿瘤免疫治疗的机制及临床应用研究进展[J]. 肿瘤代谢与营养电子杂志, 2020 , 7(2) : 145 -150 . DOI: 10.16689/j.cnki.cn11-9349/r.2020.02.003

Abstract

Tumor immunotherapy has become the new frontier of cancer therapy after surgery, chemotherapy and radiotherapy. Application of this therapeutics has generated extraordinary breakthroughs in some epithelial tumors and hematological tumors. However, there are currently two main problems in its clinical application, namely common adverse reactions and inadequate response rate in some solid tumors. With the advancement of genomics and metabolomics, people begin to appreciate the roles of gut microbiota in cancer development and treatment. The microbial community may affect the tumor immunity by modulating the host immune system and tumor microenvironment in which some microbes play antitumor roles by activating immunity while others mediate immune suppression to help cancer cells escape from the immune system. A growing body of studies have revealed that the efficacy and complications of immunotherapy are related to the gut microbiota in patients and that the hosts who are responsive to immunotherapy or prone to adverse reactions have certain microbiome traits. These microbial variables may be employed as biomarkers to predict the prognosis of immunotherapy or they may be developed as “immune-potentiators” (such as Akkermansia muciniphila and Bifidobacteria) to assist immunotherapy. A number of pre-clinical and clinical trials have demonstrated that microbial interventions including fecal microbiota transplantation can to a certain extent improve the sensitivity or reduce side effects of immunotherapy. With the development of gene editing and nanotechnology, it has been a new field of active interest to develop immunotherapy-friendly engineered bacteria. Taking advantage of the intricate relationship between intestinal flora and immunotherapy, we are hoping to mine microbial information and develop appropriate and actionable microbial interventions, thereby optimizing and making new headways in the immune-based therapeutics.

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