{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:27:12Z","timestamp":1761092832508,"version":"build-2065373602"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2019R1A6A1A03032869","2019R1A6A1A03032869","2019R1A6A1A03032869","2019R1A6A1A03032869","2019R1A6A1A03032869","2019R1A6A1A03032869"],"award-info":[{"award-number":["2019R1A6A1A03032869","2019R1A6A1A03032869","2019R1A6A1A03032869","2019R1A6A1A03032869","2019R1A6A1A03032869","2019R1A6A1A03032869"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003653","name":"Korea National Institute of Health","doi-asserted-by":"publisher","award":["2023-ER2107-00","2023-ER2107-00","2023-ER2107-00","2023-ER2107-00","2023-ER2107-00","2023-ER2107-00"],"award-info":[{"award-number":["2023-ER2107-00","2023-ER2107-00","2023-ER2107-00","2023-ER2107-00","2023-ER2107-00","2023-ER2107-00"]}],"id":[{"id":"10.13039\/501100003653","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>A unique strain of <jats:italic>Staphylococcus epidermidis<\/jats:italic>, AIT01 (AIT, Airway Immune Trainer), identified in our previous research, has demonstrated immune-boosting properties. This study aimed to evaluate the systemic immune-modulatory effects and potential anti-tumor properties of this immune-enhancing skin microbiota strain. A series of ex vivo and in vivo experiments were conducted to assess immune cell proliferation, cytokine production, and anti-tumor efficacy. In ex vivo studies, splenocytes treated with the bacterial lysate or culture supernatant of the strain showed significantly increased viability in a concentration-dependent manner. Flow cytometry analysis revealed increased populations of dendritic cells, NK cells (Natural killer cells), and \u03b3\u03b4 T cells, with enhanced cytokine production, particularly IFN-\u03b3 (Interferon-\u03b3) and perforin, in the lysate-treated group. When administered via intraperitoneal and intravenous routes in vivo, mice showed significant inhibition of melanoma growth upon receiving the bacterial lysate. Notably, pre-treatment demonstrated superior efficacy compared to post-treatment. Furthermore, the combination of the bacterial lysate with anti-PD-1 (anti-Programmed cell death protein-1) monoclonal antibody further suppressed tumor growth compared to anti-PD-1 monotherapy. These findings suggest that the AIT01 lysate enhances immune cell proliferation and cytokine production, contributing to its potent anti-tumor effects. The systemic delivery of this immune-boosting skin microbiota strain, particularly in combination with anti-PD-1 therapy, holds promise as an effective immunotherapeutic strategy against melanoma.<\/jats:p>","DOI":"10.1038\/s41598-025-20581-x","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T09:21:34Z","timestamp":1761038494000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enhancing melanoma treatment through systemic delivery of an immune boosting Staphylococcus epidermidis strain"],"prefix":"10.1038","volume":"15","author":[{"given":"Jeewon","family":"Hwang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gwanghee","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoojin","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed","family":"Ali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junho","family":"Cho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang Sun","family":"Yoon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,10,21]]},"reference":[{"key":"20581_CR1","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1038\/s41579-020-0433-9","volume":"19","author":"Y Fan","year":"2021","unstructured":"Fan, Y. & Pedersen, O. Gut microbiota in human metabolic health and disease. Nat. Rev. Microbiol. 19, 55\u201371 (2021).","journal-title":"Nat. Rev. Microbiol."},{"key":"20581_CR2","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1126\/science.aaa4972","volume":"348","author":"WS Garrett","year":"2015","unstructured":"Garrett, W. S. Cancer and the microbiota. Science 348, 80\u201386 (2015).","journal-title":"Science"},{"key":"20581_CR3","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1186\/s40168-019-0691-9","volume":"7","author":"HJ Kim","year":"2019","unstructured":"Kim, H. J. et al. Nasal commensal Staphylococcus epidermidis enhances interferon-\u03bb-dependent immunity against influenza virus. Microbiome 7, 80 (2019).","journal-title":"Microbiome"},{"key":"20581_CR4","doi-asserted-by":"publisher","first-page":"3563","DOI":"10.3390\/cancers14153563","volume":"14","author":"A Aghamajidi","year":"2022","unstructured":"Aghamajidi, A. & Vareki, S. M. The effect of the gut microbiota on systemic and Anti-Tumor immunity and response to systemic therapy against cancer. Cancers 14, 3563 (2022).","journal-title":"Cancers"},{"key":"20581_CR5","doi-asserted-by":"publisher","first-page":"605","DOI":"10.3390\/nu12030605","volume":"12","author":"E Sanchez-Rodriguez","year":"2020","unstructured":"Sanchez-Rodriguez, E. et al. The gut microbiota and its implication in the development of atherosclerosis and related cardiovascular diseases. Nutrients 12, 605 (2020).","journal-title":"Nutrients"},{"key":"20581_CR6","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1136\/gutjnl-2011-300784","volume":"61","author":"JJ Farrell","year":"2011","unstructured":"Farrell, J. J. et al. Variations of oral microbiota are associated with pancreatic diseases including pancreatic cancer. Gut 61, 582 (2011).","journal-title":"Gut"},{"key":"20581_CR7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41392-021-00710-4","volume":"7","author":"K Hou","year":"2022","unstructured":"Hou, K. et al. Microbiota in health and diseases. Signal. Transduct. Target. Ther. 7, 1\u201328 (2022).","journal-title":"Signal. Transduct. Target. Ther."},{"key":"20581_CR8","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1038\/s41591-022-01779-2","volume":"28","author":"EM Park","year":"2022","unstructured":"Park, E. M. et al. Targeting the gut and tumor microbiota in cancer. Nat. Med. 28, 690\u2013703 (2022).","journal-title":"Nat. Med."},{"key":"20581_CR9","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/s40364-022-00381-5","volume":"10","author":"J Liu","year":"2022","unstructured":"Liu, J. & Zhang, Y. Intratumor Microbiome in cancer progression: current developments, challenges and future trends. Biomark. Res. 10, 37 (2022).","journal-title":"Biomark. Res."},{"key":"20581_CR10","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1126\/science.aay9189","volume":"368","author":"D Nejman","year":"2020","unstructured":"Nejman, D. et al. The human tumor Microbiome is composed of tumor type\u2013specific intracellular bacteria. Science 368, 973\u2013980 (2020).","journal-title":"Science"},{"key":"20581_CR11","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1136\/gutjnl-2020-323426","volume":"71","author":"W Si","year":"2021","unstructured":"Si, W. et al. Lactobacillus rhamnosus GG induces cGAS\/STING- dependent type I interferon and improves response to immune checkpoint Blockade. Gut 71, 521 (2021).","journal-title":"Gut"},{"key":"20581_CR12","doi-asserted-by":"publisher","first-page":"1311","DOI":"10.1016\/j.jcmgh.2021.06.001","volume":"12","author":"JA Owens","year":"2021","unstructured":"Owens, J. A. et al. Lactobacillus rhamnosus GG orchestrates an antitumor immune response. Cell. Mol. Gastroenterol. Hepatol. 12, 1311 (2021).","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"20581_CR13","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1038\/s41423-020-0488-6","volume":"17","author":"Y Zhang","year":"2020","unstructured":"Zhang, Y. & Zhang, Z. The history and advances in cancer immunotherapy: Understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications. Cell. Mol. Immunol. 17, 807\u2013821 (2020).","journal-title":"Cell. Mol. Immunol."},{"key":"20581_CR14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s12276-018-0191-1","volume":"50","author":"P Darvin","year":"2018","unstructured":"Darvin, P., Toor, S. M., Nair, S., Elkord, E. & V. & Immune checkpoint inhibitors: recent progress and potential biomarkers. Exp. Mol. Med. 50, 1\u201311 (2018).","journal-title":"Exp. Mol. Med."},{"key":"20581_CR15","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1517\/14712598.2013.770836","volume":"13","author":"O Hamid","year":"2013","unstructured":"Hamid, O. & Carvajal, R. D. Anti-programmed death-1 and anti-programmed death-ligand 1 antibodies in cancer therapy. Expert Opin. Biol. Ther. 13, 847\u2013861 (2013).","journal-title":"Expert Opin. Biol. Ther."},{"key":"20581_CR16","doi-asserted-by":"publisher","first-page":"86","DOI":"10.3389\/fonc.2018.00086","volume":"8","author":"JA Seidel","year":"2018","unstructured":"Seidel, J. A., Otsuka, A. & Kabashima, K. Anti-PD-1 and Anti-CTLA-4 therapies in cancer: mechanisms of Action, Efficacy, and limitations. Front. Oncol. 8, 86 (2018).","journal-title":"Front. Oncol."},{"key":"20581_CR17","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1046\/j.0022-202x.2001.00043.x","volume":"6","author":"K Chiller","year":"2001","unstructured":"Chiller, K., Selkin, B. A. & Murakawa, G. J. Skin microflora and bacterial infections of the skin. J. Investig Dermatol. Symp. Proc. 6, 170\u2013174 (2001).","journal-title":"J. Investig Dermatol. Symp. Proc."},{"key":"20581_CR18","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1101\/gr.075549.107","volume":"18","author":"EA Grice","year":"2008","unstructured":"Grice, E. A. et al. A diversity profile of the human skin microbiota. Genome Res. 18, 1043 (2008).","journal-title":"Genome Res."},{"key":"20581_CR19","doi-asserted-by":"crossref","unstructured":"Fierer, N., Hamady, M., Lauber, C. L. & Knight, R. The influence of sex, handedness, and washing on the diversity of hand surface bacteria. Proc. Natl. Acad. Sci. U. S. A. 105, 17994 (2008).","DOI":"10.1073\/pnas.0807920105"},{"key":"20581_CR20","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1111\/j.1365-2133.2008.08437.x","volume":"158","author":"AL Cogen","year":"2008","unstructured":"Cogen, A. L., Nizet, V. & Gallo, R. L. Skin microbiota: a source of disease or defence? Br. J. Dermatol. 158, 442 (2008).","journal-title":"Br. J. Dermatol."},{"key":"20581_CR21","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1038\/nrmicro.2017.157","volume":"16","author":"AL Byrd","year":"2018","unstructured":"Byrd, A. L., Belkaid, Y. & Segre, J. A. The human skin Microbiome. Nat. Rev. Microbiol. 16, 143\u2013155 (2018).","journal-title":"Nat. Rev. Microbiol."},{"key":"20581_CR22","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1016\/j.smim.2013.09.005","volume":"25","author":"JA Sanford","year":"2013","unstructured":"Sanford, J. A. & Gallo, R. L. Functions of the skin microbiota in health and disease. Semin Immunol. 25, 370 (2013).","journal-title":"Semin Immunol."},{"key":"20581_CR23","doi-asserted-by":"publisher","first-page":"e31","DOI":"10.4110\/in.2023.23.e31","volume":"23","author":"G Kim","year":"2023","unstructured":"Kim, G. et al. A moonlighting protein secreted by a nasal Microbiome fortifies the innate host defense against bacterial and viral infections. Immune Netw. 23, e31 (2023).","journal-title":"Immune Netw."},{"key":"20581_CR24","doi-asserted-by":"publisher","first-page":"5949","DOI":"10.1111\/jcmm.14415","volume":"23","author":"C Leonel","year":"2019","unstructured":"Leonel, C. et al. Staphylococcus epidermidis role in the skin microenvironment. J. Cell. Mol. Med. 23, 5949 (2019).","journal-title":"J. Cell. Mol. Med."},{"key":"20581_CR25","doi-asserted-by":"publisher","first-page":"eaao4502","DOI":"10.1126\/sciadv.aao4502","volume":"4","author":"T Nakatsuji","year":"2018","unstructured":"Nakatsuji, T. et al. A commensal strain of Staphylococcus epidermidis protects against skin neoplasia. Sci. Adv. 4, eaao4502 (2018).","journal-title":"Sci. Adv."},{"key":"20581_CR26","doi-asserted-by":"publisher","first-page":"782852","DOI":"10.3389\/fimmu.2021.782852","volume":"12","author":"GAF Vitiello","year":"2021","unstructured":"Vitiello, G. A. F., Ferreira, W. A. S., de Lima, V. C. C. & Medina, T. Da S. Antiviral responses in cancer: boosting antitumor immunity through activation of interferon pathway in the tumor microenvironment. Front. Immunol. 12, 782852 (2021).","journal-title":"Front. Immunol."},{"key":"20581_CR27","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/s41586-019-1593-5","volume":"574","author":"O Demaria","year":"2019","unstructured":"Demaria, O. et al. Harnessing innate immunity in cancer therapy. Nature 574, 45\u201356 (2019).","journal-title":"Nature"},{"key":"20581_CR28","doi-asserted-by":"publisher","first-page":"550946","DOI":"10.3389\/fimmu.2020.550946","volume":"11","author":"I Pastar","year":"2020","unstructured":"Pastar, I. et al. Staphylococcus epidermidis boosts innate immune response by activation of gamma delta T cells and induction of Perforin-2 in human skin. Front. Immunol. 11, 550946 (2020).","journal-title":"Front. Immunol."},{"key":"20581_CR29","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/s12943-023-01722-0","volume":"22","author":"Z Gao","year":"2023","unstructured":"Gao, Z. et al. Gamma delta T-cell-based immune checkpoint therapy: attractive candidate for antitumor treatment. Mol. Cancer. 22, 31 (2023).","journal-title":"Mol. Cancer"},{"key":"20581_CR30","doi-asserted-by":"publisher","first-page":"16348","DOI":"10.1074\/jbc.RA118.004549","volume":"293","author":"CS Backes","year":"2018","unstructured":"Backes, C. S. et al. Natural killer cells induce distinct modes of cancer cell death: Discrimination, quantification, and modulation of apoptosis, necrosis, and mixed forms. J. Biol. Chem. 293, 16348 (2018).","journal-title":"J. Biol. Chem."},{"key":"20581_CR31","doi-asserted-by":"publisher","first-page":"4871","DOI":"10.1038\/s41467-019-12771-9","volume":"10","author":"L Huang","year":"2019","unstructured":"Huang, L. et al. Mild photothermal therapy potentiates anti-PD-L1 treatment for immunologically cold tumors via an all-in-one and all-in-control strategy. Nat. Commun. 10, 4871 (2019).","journal-title":"Nat. Commun."},{"key":"20581_CR32","doi-asserted-by":"publisher","first-page":"1493","DOI":"10.3390\/vaccines10091493","volume":"10","author":"AG Mukherjee","year":"2022","unstructured":"Mukherjee, A. G. et al. Role of immune cells and receptors in cancer treatment: an immunotherapeutic approach. Vaccines 10, 1493 (2022).","journal-title":"Vaccines"},{"key":"20581_CR33","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1038\/s41577-020-0306-5","volume":"20","author":"AD Waldman","year":"2020","unstructured":"Waldman, A. D., Fritz, J. M. & Lenardo, M. J. A guide to cancer immunotherapy: from T cell basic science to clinical practice. Nat. Rev. Immunol. 20, 651\u2013668 (2020).","journal-title":"Nat. Rev. Immunol."},{"key":"20581_CR34","doi-asserted-by":"publisher","first-page":"e141","DOI":"10.1038\/emm.2014.114","volume":"47","author":"SR Yoon","year":"2015","unstructured":"Yoon, S. R., Kim, T. D. & Choi, I. Understanding of molecular mechanisms in natural killer cell therapy. Exp. Mol. Med. 47, e141\u2013e141 (2015).","journal-title":"Exp. Mol. Med."},{"key":"20581_CR35","doi-asserted-by":"publisher","first-page":"3059","DOI":"10.3389\/fimmu.2018.03059","volume":"9","author":"C Fu","year":"2018","unstructured":"Fu, C., Jiang, A. & Dendritic Cells CD8 T cell immunity in tumor microenvironment. Front. Immunol. 9, 3059 (2018).","journal-title":"Front. Immunol."},{"key":"20581_CR36","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1126\/science.abb5920","volume":"371","author":"EN Baruch","year":"2021","unstructured":"Baruch, E. N. et al. Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients. Science 371, 602\u2013609 (2021).","journal-title":"Science"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-20581-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-20581-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-20581-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T09:21:37Z","timestamp":1761038497000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-20581-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,21]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["20581"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-20581-x","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,21]]},"assertion":[{"value":"30 October 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"36697"}}