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| Progress on the mechanism and clinical application of gut microbiota in tumor immunotherapy |
| Zhang Xueying， Qin Huanlong |
| 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 |
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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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