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      Microbiota and Lung Cancer. Opportunities and Challenges for Improving Immunotherapy Efficacy

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          The advances in molecular biology and the emergence of Next Generation Sequencing (NGS) have revealed that microbiome composition is closely related with health and disease, including cancer. This relationship affects different levels of cancer such as development, progression, and response to treatment including immunotherapy. The efficacy of immune checkpoint inhibitors (ICIs) may be influenced by the concomitant use of antibiotics before, during or shortly after treatment with ICIs. Nevertheless, the linking mechanism between microbiote, host immunity and cancer is not clear and the role of microbiota manipulation and analyses in cancer management has not been clinically validated yet. Regarding the use of microbiome as biomarker to predict ICI efficacy it has been recently shown that the use of biochemical serum markers to monitor intestinal permeability and loss of barrier integrity, like citrulline, could be useful to monitor microbiota changes and predict ICI efficacy. There are still many unknowns about the role of these components, their relationship with the microbiota, with the use of antibiotics and the response to immunotherapy. The next challenge in microbiome research will be to identify individual microbial species that causally affect lung cancer phenotypes and response to ICI and disentangle the underlying mechanisms. Thus, further analyses in patients with lung cancer receiving treatment with ICIs and its correlation with the composition of the microbiota in different organs including the respiratory tract, peripheral blood and intestinal tract could be useful to predict the efficacy of ICIs and its modulation with antibiotic use.

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          Most cited references 90

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          Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

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            Nivolumab versus Docetaxel in Advanced Nonsquamous Non–Small-Cell Lung Cancer

            Nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, disrupts PD-1-mediated signaling and may restore antitumor immunity.
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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.

                Author and article information

                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                24 September 2020
                : 10
                1Medical Oncology Department, Lozano Blesa University Clinical Hospital , Zaragoza, Spain
                2Instituto de Investigación Sanitaria Aragón (IIS Aragón) , Zaragoza, Spain
                3Inmunology Department, Lozano Blesa University Clinical Hospital , Zaragoza, Spain
                4Department of Microbiology, Pediatrics, Radiology and Public Health, University of Zaragoza , Zaragoza, Spain
                5Aragon Nanoscience Institute , Zaragoza, Spain
                6Aragon Materials Science Institute , Zaragoza, Spain
                7Unidad de Nanotoxicología e Inmunotoxicología (UNATI), Fundación Instituto de Investigación Sanitaria Aragón (IIS Aragón), Biomedical Research Centre of Aragón (CIBA) , Zaragoza, Spain
                8Infectious Diseases Department, Lozano Blesa University Clinical Hospital , Zaragoza, Spain
                9ARAID Foundation (IIS Aragón) , Zaragoza, Spain
                10Microbiology, Preventive Medicine and Public Health Department, Medicine, University of Zaragoza , Zaragoza, Spain
                11Biomedical Research Center in Bioengineering, Biomaterials and Nanomedicine Network (CIBER-BBN) , Madrid, Spain
                12Instituto de Carboquimica (ICB-Consejo Superior de Investigaciones Cientificas) , Zaragoza, Spain
                Author notes

                Edited by: Kartik Sehgal, Beth Israel Deaconess Medical Center and Harvard Medical School, United States

                Reviewed by: James Tsay, New York University, United States; Marcello Tiseo, University Hospital of Parma, Italy

                *Correspondence: Maitane Ocáriz-Díez mocarizdiez@

                This article was submitted to Thoracic Oncology, a section of the journal Frontiers in Oncology

                Copyright © 2020 Ocáriz-Díez, Cruellas, Gascón, Lastra, Martínez-Lostao, Ramírez-Labrada, Paño, Sesma, Torres, Yubero, Pardo, Isla and Gálvez.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 90, Pages: 8, Words: 7428
                Funded by: Bristol-Myers Squibb 10.13039/100002491
                Funded by: European Regional Development Fund 10.13039/501100008530
                Funded by: Ministerio de Ciencia, Innovación y Universidades 10.13039/100014440
                Funded by: Fundación Agencia Aragonesa para la Investigación y el Desarrollo 10.13039/501100008767
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                Oncology & Radiotherapy

                antibiotics, microbiota, lung cancer, immunotherapy, lung microbiota


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