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      The role of gut microbiota in cancer treatment: friend or foe?

      review-article
      1 , 2 , 1 ,
      Gut
      BMJ Publishing Group
      intestinal microbiology, cancer

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          Abstract

          The gut microbiota has been implicated in cancer and shown to modulate anticancer drug efficacy. Altered gut microbiota is associated with resistance to chemo drugs or immune checkpoint inhibitors (ICIs), whereas supplementation of distinct bacterial species restores responses to the anticancer drugs. Accumulating evidence has revealed the potential of modulating the gut microbiota to enhance the efficacy of anticancer drugs. Regardless of the valuable findings by preclinical models and clinical data of patients with cancer, a more thorough understanding of the interactions of the microbiota with cancer therapy helps researchers identify novel strategy for cancer prevention, stratify patients for more effective treatment and reduce treatment complication. In this review, we discuss the scientific evidence on the role of gut microbiota in cancer treatment, and highlight the latest knowledge and technologies leveraged to target specific bacteria that contribute to tumourigenesis. First, we provide an overview of the role of the gut microbiota in cancer, establishing the links between bacteria, inflammation and cancer treatment. Second, we highlight the mechanisms used by distinct bacterial species to modulate cancer growth, immune responses, as well as the efficacy of chemotherapeutic drugs and ICIs. Third, we demonstrate various approaches to modulate the gut microbiota and their potential in translational research. Finally, we discuss the limitations of current microbiome research in the context of cancer treatment, ongoing efforts to overcome these challenges and future perspectives.

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          Most cited references58

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          Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab

          Ipilimumab, an immune checkpoint inhibitor targeting CTLA-4, prolongs survival in a subset of patients with metastatic melanoma (MM) but can induce immune-related adverse events, including enterocolitis. We hypothesized that baseline gut microbiota could predict ipilimumab anti-tumor response and/or intestinal toxicity.
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            Human Primary Liver Cancer -derived Organoid Cultures for disease modelling and drug screening

            Human liver cancer research currently lacks in vitro models that faithfully recapitulate the pathophysiology of the original tumour. We recently described a novel, near-physiological organoid culture system, where primary human healthy liver cells form long-term expanding organoids that retain liver tissue function and genetic stability. Here, we extend this culture system to the propagation of primary liver cancer (PLC) organoids from three of the most common PLC subtypes: hepatocellular carcinoma (HCC), cholangiocarcinoma (CC) and combined HCC/CC (CHC) tumours. PLC-derived organoid cultures preserve the histological architecture, gene expression and genomic landscape of the original tumour, allowing discrimination between different tumour tissues and subtypes, even after long term expansion in culture in the same medium conditions. Xenograft studies demonstrate that the tumourogenic potential, histological features and metastatic properties of PLC-derived organoids are preserved in vivo. PLC-derived organoids are amenable for biomarker identification and drug screening testing and lead to the identification of the ERK inhibitor SCH772984 as a potential therapeutic agent for primary liver cancer. We thus demonstrate the wide-ranging biomedical utilities of PLC-derived organoid models in furthering the understanding of liver cancer biology and in developing personalized medicine approaches for the disease.
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              A defined commensal consortium elicits CD8 T cells and anti-cancer immunity

              There is a growing appreciation for the importance of the gut microbiota as a therapeutic target in various diseases. However, there are only a handful of known commensal strains that can potentially be used to manipulate host physiological functions. Here we isolate a consortium of 11 bacterial strains from healthy human donor faeces that is capable of robustly inducing interferon-γ-producing CD8 T cells in the intestine. These 11 strains act together to mediate the induction without causing inflammation in a manner that is dependent on CD103+ dendritic cells and major histocompatibility (MHC) class Ia molecules. Colonization of mice with the 11-strain mixture enhances both host resistance against Listeria monocytogenes infection and the therapeutic efficacy of immune checkpoint inhibitors in syngeneic tumour models. The 11 strains primarily represent rare, low-abundance components of the human microbiome, and thus have great potential as broadly effective biotherapeutics.
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                Author and article information

                Journal
                Gut
                Gut
                gutjnl
                gut
                Gut
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                0017-5749
                1468-3288
                October 2020
                5 August 2020
                : 69
                : 10
                : 1867-1876
                Affiliations
                [1 ] departmentState Key Laboratory of Digestive Disease, Institute of Digestive Disease and The Department of Medicine and Therapeutics , Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong , Hong Kong SAR, China
                [2 ] departmentDivision of Translational Research, Department of Medical Research , Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Biomedical Bioinformatics and School of Medicine, National Yang-Ming University, Taipei, Taiwan; College of Public Health and Graduate Institute of Clinical Medicine, China Medical University , Taichung, Taiwan
                Author notes
                [Correspondence to ] Dr Jun Yu, Institute of Digestive Disease and The Department of Medicine and Therapeutics, Chinese University of Hong Kong, New Territories, Hong Kong; junyu@ 123456cuhk.edu.hk
                Author information
                http://orcid.org/0000-0001-5008-2153
                Article
                gutjnl-2020-321153
                10.1136/gutjnl-2020-321153
                7497589
                32759302
                c0716e52-5498-4f41-aada-066a2d327f46
                © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:  http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 18 March 2020
                : 02 July 2020
                : 06 July 2020
                Categories
                Recent Advances in Basic Science
                1506
                2312
                1239
                Custom metadata
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                Gastroenterology & Hepatology
                intestinal microbiology,cancer
                Gastroenterology & Hepatology
                intestinal microbiology, cancer

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