活菌药物在肿瘤免疫治疗中的应用进展和未来展望

张宇龙,许晓敏,阳奕琰,尹意铭,郝淮杰,寇岩,谭验

肿瘤代谢与营养电子杂志 ›› 2021, Vol. 8 ›› Issue (2) : 198-204.

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肿瘤代谢与营养电子杂志 ›› 2021, Vol. 8 ›› Issue (2) : 198-204.
综述

活菌药物在肿瘤免疫治疗中的应用进展和未来展望

  • 肠道微生物是人体重要的器官,在人类健康和疾病中发挥重要作用。很多疾病被证实与肠道微生物的组成和功能 改变相关。肿瘤免疫治疗作为一种新兴的肿瘤治疗手段,具有特异性强、疗效显著等特点,免疫检查点抑制剂是目前应用较为 广泛的方法之一。免疫检测点抑制剂的疗效与肠道菌群有直接联系。本文对近年来肿瘤免疫治疗相关肠道微生物的研究进 展进行总结,阐述了肠道菌群在肿瘤治疗中的功能和作用机制,如通过代谢产物或表面蛋白直接或间接抑制肿瘤生长或诱导 肿瘤细胞凋亡,调节免疫系统特别是肿瘤微环境发挥抗肿瘤功能等。随着HUMAnN2流程、DADA2流程、metaWRAP等生物信 息工具和统计方法在肠道菌群方面的应用,肠道菌群在肿瘤免疫方面的研究得到进一步发展。目前,各研究机构和生物制药 公司均已在肠道微生物领域进行规划,并已注册多项临床试验。本文还就免疫治疗相关肠道微生物的发现方法以及用于肿瘤 免疫治疗的活菌药物开发进展情况进行介绍,并在此基础上探讨了目前的缺陷和未来的发展趋势。
作者信息 +

The progress and prospects of live biotherapeutics on cancer immunotherapy

  • The gut microbiota is considered an indispensable organ and plays an important role in human health. Numbers of diseases ranging from chronic inflammatory, metabolic diseases to neurological disorders and cancer were associated with the compositional and functional changes in the gut microbiota. Cancer immunotherapy such as immune checkpoint inhibitor (ICI) is an emerging treatment with high specificity and efficacious. Recent studies showed that the efficacy of ICIs in patients with cancer was associated with the gut microbiota. In this review, we summarized studies on cancer immunotherapy?associated gut microbes, including the function of the gut microbiota in cancer immunotherapy, the potential mechanisms on how it affects the cancer immunotherapy. For example, metabolites and surface proteins of gut microbes could inhibit tumor growth or induce the apoptosis of tumor via direct or indirect mechanisms, or modulate the immune system especially in the tumor microenvironment. The development of bioinformatic tools and statistical approaches along with the application in the analysis of gut microbiota accelerated the discovery of new gut microbes associated with cancer immunotherapy. Up to now, there are several organizations and pharmaceutical companies involving in the development of live biotherapeutic products targeting cancer immunotherapy. Numerous clinical trials have been registered and launched based on the fundamental researches on gut microbiota. In this review, we also summarized the computational methods for identifying candidate therapeutic bacterium, as well as the development of live therapeutics on cancer immunotherapy. We also discussed the challenges of current live therapeutics discoveries on cancer immunotherapy and prospective development trends.
Author information +
文章历史 +

摘要

肠道微生物是人体重要的器官,在人类健康和疾病中发挥重要作用。很多疾病被证实与肠道微生物的组成和功能 改变相关。肿瘤免疫治疗作为一种新兴的肿瘤治疗手段,具有特异性强、疗效显著等特点,免疫检查点抑制剂是目前应用较为 广泛的方法之一。免疫检测点抑制剂的疗效与肠道菌群有直接联系。本文对近年来肿瘤免疫治疗相关肠道微生物的研究进 展进行总结,阐述了肠道菌群在肿瘤治疗中的功能和作用机制,如通过代谢产物或表面蛋白直接或间接抑制肿瘤生长或诱导 肿瘤细胞凋亡,调节免疫系统特别是肿瘤微环境发挥抗肿瘤功能等。随着HUMAnN2流程、DADA2流程、metaWRAP等生物信 息工具和统计方法在肠道菌群方面的应用,肠道菌群在肿瘤免疫方面的研究得到进一步发展。目前,各研究机构和生物制药 公司均已在肠道微生物领域进行规划,并已注册多项临床试验。本文还就免疫治疗相关肠道微生物的发现方法以及用于肿瘤 免疫治疗的活菌药物开发进展情况进行介绍,并在此基础上探讨了目前的缺陷和未来的发展趋势。

Abstract

The gut microbiota is considered an indispensable organ and plays an important role in human health. Numbers of diseases ranging from chronic inflammatory, metabolic diseases to neurological disorders and cancer were associated with the compositional and functional changes in the gut microbiota. Cancer immunotherapy such as immune checkpoint inhibitor (ICI) is an emerging treatment with high specificity and efficacious. Recent studies showed that the efficacy of ICIs in patients with cancer was associated with the gut microbiota. In this review, we summarized studies on cancer immunotherapy⁃associated gut microbes, including the function of the gut microbiota in cancer immunotherapy, the potential mechanisms on how it affects the cancer immunotherapy. For example, metabolites and surface proteins of gut microbes could inhibit tumor growth or induce the apoptosis of tumor via direct or indirect mechanisms, or modulate the immune system especially in the tumor microenvironment. The development of bioinformatic tools and statistical approaches along with the application in the analysis of gut microbiota accelerated the discovery of new gut microbes associated with cancer immunotherapy. Up to now, there are several organizations and pharmaceutical companies involving in the development of live biotherapeutic products targeting cancer immunotherapy. Numerous clinical trials have been registered and launched based on the fundamental researches on gut microbiota. In this review, we also summarized the computational methods for identifying candidate therapeutic bacterium, as well as the development of live therapeutics on cancer immunotherapy. We also discussed the challenges of current live therapeutics discoveries on cancer immunotherapy and prospective development trends.

关键词

活菌药物 / 肿瘤免疫治疗 / 肠道菌群

Key words

Live biotherapeutics / Cancer immunotherapy / Gut microbiota

引用本文

导出引用
张宇龙,许晓敏,阳奕琰,尹意铭,郝淮杰,寇岩,谭验. 活菌药物在肿瘤免疫治疗中的应用进展和未来展望[J]. 肿瘤代谢与营养电子杂志. 2021, 8(2): 198-204
Zhang Yulong, Xu Xiaomin, Yang Yiyan, Yin Yiming, Hao Huaijie, Kou Yan, Tan Yan. The progress and prospects of live biotherapeutics on cancer immunotherapy[J]. Electronic Journal of Metabolism and Nutrition of Cancer. 2021, 8(2): 198-204

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