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      Skin Microbiome and Treatment-Related Skin Toxicities in Patients With Cancer: A Mini-Review

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          Abstract

          The human skin hosts millions of bacteria, fungi, archaea, and viruses. These skin microbes play a crucial role in human immunological and physiological functions, as well as the development of skin diseases, including cancer when the balance between skin commensals and pathogens is interrupted. Due to the linkages between inflammation processes and skin microbes, and viral links to skin cancer, new theories have supported the role a dysbiotic skin microbiome plays in the development of cancer and cancer treatment-related skin toxicities. This review focuses on the skin microbiome and its role in cancer treatment-related skin toxicities, particularly from chemotherapy, radiation therapy, and immunotherapy. The current literature found changes in the diversity and abundance of the skin microbiome during cancer treatments such as radiation therapy, including lower diversity of the skin microbiome, an increased Proteobacteria/Firmicutes ratio, and a higher abundance of pathogenic Staphylococcus aureus. These changes may be associated with the development and severity of treatment-related skin toxicities, such as acute radiation dermatitis, hand-foot syndrome in chemotherapy, and immunotherapy-induced rash. Several clinical guidelines have issued potential interventions (e.g., use of topical corticosteroids, phototherapy, and non-pharmaceutical skin care products) to prevent and treat skin toxicities. The effectiveness of these promising interventions in alleviating treatment-related skin toxicities should be further tested among cancer patients.

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          Most cited references77

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          The human skin microbiome

          Functioning as the exterior interface of the human body with the environment, skin acts as a physical barrier to prevent the invasion of foreign pathogens while providing a home to the commensal microbiota. The harsh physical landscape of skin, particularly the desiccated, nutrient-poor, acidic environment, also contributes to the adversity that pathogens face when colonizing human skin. Despite this, the skin is colonized by a diverse microbiota. In this Review, we describe amplicon and shotgun metagenomic DNA sequencing studies that have been used to assess the taxonomic diversity of microorganisms that are associated with skin from the kingdom to the strain level. We discuss recent insights into skin microbial communities, including their composition in health and disease, the dynamics between species and interactions with the immune system, with a focus on Propionibacterium acnes, Staphylococcus epidermidis and Staphylococcus aureus.
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            Topographical and temporal diversity of the human skin microbiome.

            Human skin is a large, heterogeneous organ that protects the body from pathogens while sustaining microorganisms that influence human health and disease. Our analysis of 16S ribosomal RNA gene sequences obtained from 20 distinct skin sites of healthy humans revealed that physiologically comparable sites harbor similar bacterial communities. The complexity and stability of the microbial community are dependent on the specific characteristics of the skin site. This topographical and temporal survey provides a baseline for studies that examine the role of bacterial communities in disease states and the microbial interdependencies required to maintain healthy skin.
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              Binding of the Fap2 protein of Fusobacterium nucleatum to human inhibitory receptor TIGIT protects tumors from immune cell attack.

              Bacteria, such as Fusobacterium nucleatum, are present in the tumor microenvironment. However, the immunological consequences of intra-tumoral bacteria remain unclear. Here, we have shown that natural killer (NK) cell killing of various tumors is inhibited in the presence of various F. nucleatum strains. Our data support that this F. nucleatum-mediated inhibition is mediated by human, but not by mouse TIGIT, an inhibitory receptor present on all human NK cells and on various T cells. Using a library of F. nucleatum mutants, we found that the Fap2 protein of F. nucleatum directly interacted with TIGIT, leading to the inhibition of NK cell cytotoxicity. We have further demonstrated that tumor-infiltrating lymphocytes expressed TIGIT and that T cell activities were also inhibited by F. nucleatum via Fap2. Our results identify a bacterium-dependent, tumor-immune evasion mechanism in which tumors exploit the Fap2 protein of F. nucleatum to inhibit immune cell activity via TIGIT.
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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
                15 July 2022
                2022
                : 12
                : 924849
                Affiliations
                [1] 1 Emory College, Emory University , Atlanta, GA, United States
                [2] 2 Department of Radiation Oncology, Winship Cancer Institute, School of Medicine, Emory University , Atlanta, GA, United States
                [3] 3 Nell Hodgson Woodruff School of Nursing, Emory University , Atlanta, GA, United States
                Author notes

                Edited by: Ilaria Grazia Zizzari, Sapienza University of Rome, Italy

                Reviewed by: Shigefumi Okamoto, Kanazawa University, Japan; Anita Y. Voigt, Jackson Laboratory for Genomic Medicine, United States

                *Correspondence: Jinbing Bai, jinbing.bai@ 123456emory.edu

                This article was submitted to Cancer Molecular Targets and Therapeutics, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2022.924849
                9334917
                35912217
                2e9bc4b5-6c26-4bd1-aedb-d8417aa035be
                Copyright © 2022 Richardson, Lin, Buchwald and Bai

                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
                : 20 April 2022
                : 23 June 2022
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 77, Pages: 8, Words: 3661
                Categories
                Oncology
                Mini Review

                Oncology & Radiotherapy
                cancer,chemotherapy,immunotherapy,radiation therapy,skin microbiome,adverse event,skin toxicity,16s rrna

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