<p>Microbiome is ubiquitous in human and distributed in not only normal organs such as gut, but also in tumor tissues of the host. Numerous studies have proven that the extratumoral microbiota (mainly gut microbiota) has a close relationship with the local and systemic immune systems of the host. The bacteria, viruses and fungi in gut can influence the activity of innate and adaptive immune cells, affecting the outcomes of immunotherapy. In addition to microbiota in the gut, special microbiota (intratumoral microbiota) exists in the tumor microenvironment (TME), which provides a critical niche for anaerobic or facultative anaerobic bacteria to colonize and proliferate. Intratumoral microorganisms or their metabolites can substantially improve the immunosuppressive of the TME, reactivate immune cells, or recruit activated immune cells, indicating a potential effect on immunotherapy. Furthermore, with the development of synthetic biology, some tumor-targeting bacteria can be used as a biological chassis for the accurate delivery of different immunotherapeutic agents to tumor core through genetic programming technologies, enriching immunotherapy paradigms. In this review, we summarize the recent developments in effect of human microbiota, especially microorganisms in the TME, on immunoregulation, and discuss their potential application in the field of cancer immunotherapy. We also describe the ways to take advantage of genetically engineered bacteria targeting the TME to strengthen the efficacy of immunotherapy against cancer. Additionally, the remaining questions and further directions for microbiota application in immunotherapy are also discussed.</p>

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