Unexpected guests in the tumor microenvironment: microbiome in cancer
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Protein & Cell
REVIEW Unexpected guests in the tumor microenvironment: microbiome in cancer Abigail Wong-Rolle1, Haohan Karen Wei2, Chen Zhao1&, Chengcheng Jin2& Thoracic and Gastrointestinal Malignancies Branch, National Cancer Institute, National Institutes of Health, 4 Memorial Drive, Bethesda, MD 20892, USA 2 Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, 421 Curie Blvd., Philadelphia, PA 19104, USA & Correspondence: [email protected] (C. Zhao), [email protected] (C. Jin) Received August 23, 2020 Accepted November 1, 2020
ABSTRACT Although intestinal microbiome have been established as an important biomarker and regulator of cancer development and therapeutic response, less is known about the role of microbiome at other body sites in cancer. Emerging evidence has revealed that the local microbiota make up an important part of the tumor microenvironment across many types of cancer, especially in cancers arising from mucosal sites, including the lung, skin and gastrointestinal tract. The populations of bacteria that reside specifically within tumors have been found to be tumor-type specific, and mechanistic studies have demonstrated that tumor-associated microbiota may directly regulate cancer initiation, progression and responses to chemo- or immuno-therapies. This review aims to provide a comprehensive review of the important literature on the microbiota in the cancerous tissue, and their function and mechanism of action in cancer development and treatment.
KEYWORDS microbiome, tumor, lung cancer, immune system, tumor-associated microbiota, cancer immunotherapy INTRODUCTION The commensal microbiome contains at least 100-fold more unique genes than the human host genome (Ley et al., 2006; Human Microbiome Project, 2012; Belkaid and Hand, 2014; Dzutsev et al., 2017). The primary habitat of the human
Abigail Wong-Rolle and Haohan Karen Wei have contributed equally.
© The Author(s) 2020
commensal microbiota is the gut, but thriving microbial populations exist throughout much of the body including the skin, oral, respiratory, and genital tracts (Human Microbiome Project, 2012). These microbes influence many of our important physiological functions including our metabolism and immune system. This metaorganism, made up of human host and microbial symbionts, senses environmental cues and adapts accordingly (Belkaid and Naik, 2013; Dzutsev et al., 2017). The complex interaction between the host and microbes extends to cancer; microorganisms are implicated in 20% of human malignancies (de Martel et al., 2012). Commensal bacteria directly affect tumorigenesis, progression and responses to treatment. Disruption of commensal gut microbiota in mice can affect the response of tumors to immunotherapy and chemotherapy (Iida et al., 2013; Viaud et al., 2013; Sivan et al., 2015; Vétizou et al., 2015). This dependence of treatment responsiveness on the gut microbiome has also been observed in cancer patients. Antibiotic treatment is associated with reduced response to
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