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

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          Abstract

          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 references90

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

          This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.
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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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              Pembrolizumab plus Chemotherapy in Metastatic Non–Small-Cell Lung Cancer

              First-line therapy for advanced non-small-cell lung cancer (NSCLC) that lacks targetable mutations is platinum-based chemotherapy. Among patients with a tumor proportion score for programmed death ligand 1 (PD-L1) of 50% or greater, pembrolizumab has replaced cytotoxic chemotherapy as the first-line treatment of choice. The addition of pembrolizumab to chemotherapy resulted in significantly higher rates of response and longer progression-free survival than chemotherapy alone in a phase 2 trial.
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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                24 September 2020
                2020
                : 10
                : 568939
                Affiliations
                [1] 1Medical Oncology Department, Lozano Blesa University Clinical Hospital , Zaragoza, Spain
                [2] 2Instituto de Investigación Sanitaria Aragón (IIS Aragón) , Zaragoza, Spain
                [3] 3Inmunology Department, Lozano Blesa University Clinical Hospital , Zaragoza, Spain
                [4] 4Department of Microbiology, Pediatrics, Radiology and Public Health, University of Zaragoza , Zaragoza, Spain
                [5] 5Aragon Nanoscience Institute , Zaragoza, Spain
                [6] 6Aragon Materials Science Institute , Zaragoza, Spain
                [7] 7Unidad de Nanotoxicología e Inmunotoxicología (UNATI), Fundación Instituto de Investigación Sanitaria Aragón (IIS Aragón), Biomedical Research Centre of Aragón (CIBA) , Zaragoza, Spain
                [8] 8Infectious Diseases Department, Lozano Blesa University Clinical Hospital , Zaragoza, Spain
                [9] 9ARAID Foundation (IIS Aragón) , Zaragoza, Spain
                [10] 10Microbiology, Preventive Medicine and Public Health Department, Medicine, University of Zaragoza , Zaragoza, Spain
                [11] 11Biomedical Research Center in Bioengineering, Biomaterials and Nanomedicine Network (CIBER-BBN) , Madrid, Spain
                [12] 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@ 123456gmail.com

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

                Article
                10.3389/fonc.2020.568939
                7552963
                33117698
                28201f18-d653-432b-89a2-219d172e6f84
                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.

                History
                : 17 June 2020
                : 26 August 2020
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 90, Pages: 8, Words: 7428
                Funding
                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
                Categories
                Oncology
                Mini Review

                Oncology & Radiotherapy
                microbiota,lung cancer,immunotherapy,lung microbiota,antibiotics
                Oncology & Radiotherapy
                microbiota, lung cancer, immunotherapy, lung microbiota, antibiotics

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