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肠道微生物组作为调节癌症免疫治疗耐药性的潜在因素。

Gut Microbiome as a Potential Factor for Modulating Resistance to Cancer Immunotherapy.

机构信息

Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.

Department of Pharmacy, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, China.

出版信息

Front Immunol. 2020 Jan 17;10:2989. doi: 10.3389/fimmu.2019.02989. eCollection 2019.

Abstract

Gut microbiota refers to the diverse community of more than 100 trillion microorganisms residing in our intestines. It is now known that any shift in the composition of gut microbiota from that present during the healthy state in an individual is associated with predisposition to multiple pathological conditions, such as diabetes, autoimmunity, and even cancer. Currently, therapies targeting programmed cell death protein 1/programmed cell death 1 ligand 1 or cytotoxic T-lymphocyte antigen-4 are the focus of cancer immunotherapy and are widely applied in clinical treatment of various tumors. Owing to relatively low overall response rate, however, it has been an ongoing research endeavor to identify the mechanisms or factors for improving the therapeutic efficacy of these immunotherapies. Other than causing mutations that affect gene expression, some gut bacteria may also activate or repress the host's response to immune checkpoint inhibitors. In this review, we have described recent advancements made in understanding the regulatory relationship between gut microbiome and cancer immunotherapy. We have also summarized the potential molecular mechanisms behind this interaction, which can serve as a basis for utilizing different kinds of gut bacteria as promising tools for reversing immunotherapy resistance in cancer.

摘要

肠道微生物群是指存在于我们肠道内的超过 1000 万亿微生物的多样化群落。现在已知,个体肠道微生物群的组成从健康状态发生任何变化,都与多种病理状况(如糖尿病、自身免疫,甚至癌症)的易感性有关。目前,针对程序性细胞死亡蛋白 1/程序性细胞死亡配体 1 或细胞毒性 T 淋巴细胞相关抗原 4 的治疗方法是癌症免疫治疗的重点,并且广泛应用于各种肿瘤的临床治疗中。然而,由于总体反应率相对较低,因此,一直在努力研究识别改善这些免疫疗法治疗效果的机制或因素。除了导致影响基因表达的突变外,一些肠道细菌还可能激活或抑制宿主对免疫检查点抑制剂的反应。在这篇综述中,我们描述了在理解肠道微生物组与癌症免疫治疗之间的调节关系方面取得的最新进展。我们还总结了这种相互作用背后的潜在分子机制,这可以为利用不同种类的肠道细菌作为逆转癌症免疫治疗耐药性的有前途的工具提供依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3d/6978681/fdea42998d14/fimmu-10-02989-g0002.jpg

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