{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T04:41:56Z","timestamp":1790052116603,"version":"4.0.1"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":79,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Immunol Immunother"],"DOI":"10.1007\/s00262-026-04480-2","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T08:08:59Z","timestamp":1782806939000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["R-5780, a SagA-engineered Lactococcus lactis, is a safe oral synthetic-biology microbial therapy that potentiates PD-1 blockade"],"prefix":"10.1007","volume":"75","author":[{"given":"Miaki","family":"Fukuhara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bikash","family":"Sahay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary R.","family":"Fanger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian Furlan","family":"Freguia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"issue":"26","key":"4480_CR1","doi-asserted-by":"publisher","first-page":"2443","DOI":"10.1056\/NEJMoa1200690","volume":"366","author":"SL Topalian","year":"2012","unstructured":"Topalian SL, Hodi FS, Brahmer JR et al (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 366(26):2443\u20132454. https:\/\/doi.org\/10.1056\/NEJMoa1200690","journal-title":"N Engl J Med"},{"issue":"1","key":"4480_CR2","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1056\/NEJMoa1504030","volume":"373","author":"J Larkin","year":"2015","unstructured":"Larkin J, Chiarion-Sileni V, Gonzalez R et al (2015) Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 373(1):23\u201334. https:\/\/doi.org\/10.1056\/NEJMoa1504030","journal-title":"N Engl J Med"},{"issue":"13","key":"4480_CR3","doi-asserted-by":"publisher","first-page":"e498","DOI":"10.1016\/s1470-2045(15)00007-8","volume":"16","author":"AB Sharabi","year":"2015","unstructured":"Sharabi AB, Lim M, DeWeese TL, Drake CG (2015) Radiation and checkpoint blockade immunotherapy: radiosensitisation and potential mechanisms of synergy. Lancet Oncol 16(13):e498-509. https:\/\/doi.org\/10.1016\/s1470-2045(15)00007-8","journal-title":"Lancet Oncol"},{"issue":"5","key":"4480_CR4","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1016\/j.cell.2017.10.003","volume":"171","author":"SB Widenmaier","year":"2017","unstructured":"Widenmaier SB, Snyder NA, Nguyen TB et al (2017) NRF1 is an ER membrane sensor that is central to cholesterol homeostasis. Cell 171(5):1094-1109.e15. https:\/\/doi.org\/10.1016\/j.cell.2017.10.003","journal-title":"Cell"},{"issue":"6371","key":"4480_CR5","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1126\/science.aan4236","volume":"359","author":"V Gopalakrishnan","year":"2018","unstructured":"Gopalakrishnan V, Spencer CN, Nezi L et al (2018) Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science 359(6371):97\u2013103. https:\/\/doi.org\/10.1126\/science.aan4236","journal-title":"Science"},{"issue":"6371","key":"4480_CR6","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1126\/science.aan3706","volume":"359","author":"B Routy","year":"2018","unstructured":"Routy B, Le Chatelier E, Derosa L et al (2018) Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 359(6371):91\u201397. https:\/\/doi.org\/10.1126\/science.aan3706","journal-title":"Science"},{"issue":"1","key":"4480_CR7","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1038\/s41522-025-00786-8","volume":"11","author":"W Lei","year":"2025","unstructured":"Lei W, Zhou K, Lei Y et al (2025) Gut microbiota shapes cancer immunotherapy responses. NPJ Biofilms Microbiomes 11(1):143. https:\/\/doi.org\/10.1038\/s41522-025-00786-8","journal-title":"NPJ Biofilms Microbiomes"},{"key":"4480_CR8","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.95297","author":"S Klupt","year":"2024","unstructured":"Klupt S, Fam KT, Zhang X et al (2024) Secreted antigen A peptidoglycan hydrolase is essential for Enterococcus faecium cell separation and priming of immune checkpoint inhibitor therapy. Elife. https:\/\/doi.org\/10.7554\/eLife.95297","journal-title":"Elife"},{"issue":"6371","key":"4480_CR9","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1126\/science.aao3290","volume":"359","author":"V Matson","year":"2018","unstructured":"Matson V, Fessler J, Bao R et al (2018) The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science 359(6371):104\u2013108. https:\/\/doi.org\/10.1126\/science.aao3290","journal-title":"Science"},{"issue":"6558","key":"4480_CR10","doi-asserted-by":"publisher","first-page":"1040","DOI":"10.1126\/science.abc9113","volume":"373","author":"ME Griffin","year":"2021","unstructured":"Griffin ME, Espinosa J, Becker JL et al (2021) Enterococcus peptidoglycan remodeling promotes checkpoint inhibitor cancer immunotherapy. Science 373(6558):1040\u20131046. https:\/\/doi.org\/10.1126\/science.abc9113","journal-title":"Science"},{"key":"4480_CR11","doi-asserted-by":"publisher","first-page":"102031","DOI":"10.1016\/j.tranon.2024.102031","volume":"46","author":"Y Zhang","year":"2024","unstructured":"Zhang Y, Zhang C, Chen G et al (2024) Subclone from CT26 resistant to anti-PD-1 therapy associated with increased expression of genes related to glucocorticoids. Transl Oncol 46:102031. https:\/\/doi.org\/10.1016\/j.tranon.2024.102031","journal-title":"Transl Oncol"},{"issue":"6","key":"4480_CR12","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1038\/ni.2035","volume":"12","author":"EJ Wherry","year":"2011","unstructured":"Wherry EJ (2011) T cell exhaustion. Nat Immunol 12(6):492\u2013499. https:\/\/doi.org\/10.1038\/ni.2035","journal-title":"Nat Immunol"},{"issue":"1","key":"4480_CR13","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1038\/ni.1679","volume":"10","author":"SD Blackburn","year":"2009","unstructured":"Blackburn SD, Shin H, Haining WN et al (2009) Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat Immunol 10(1):29\u201337. https:\/\/doi.org\/10.1038\/ni.1679","journal-title":"Nat Immunol"},{"key":"4480_CR14","doi-asserted-by":"publisher","first-page":"1255533","DOI":"10.3389\/fimmu.2023.1255533","volume":"14","author":"E Grebenciucova","year":"2023","unstructured":"Grebenciucova E, VanHaerents S (2023) Interleukin 6: at the interface of human health and disease. Front Immunol 14:1255533. https:\/\/doi.org\/10.3389\/fimmu.2023.1255533","journal-title":"Front Immunol"},{"issue":"6","key":"4480_CR15","doi-asserted-by":"publisher","first-page":"1368","DOI":"10.1021\/acschembio.3c00085","volume":"18","author":"ME Griffin","year":"2023","unstructured":"Griffin ME, Tsukidate T, Hang HC (2023) N-Arylpyrazole NOD2 agonists promote immune checkpoint inhibitor therapy. ACS Chem Biol 18(6):1368\u20131377. https:\/\/doi.org\/10.1021\/acschembio.3c00085","journal-title":"ACS Chem Biol"},{"key":"4480_CR16","doi-asserted-by":"publisher","first-page":"1836","DOI":"10.3389\/fmicb.2018.01836","volume":"9","author":"Y Zhao","year":"2018","unstructured":"Zhao Y, Shen J, Wu B et al (2018) Genotypic diversity and epidemiology of human rhinovirus among children with severe acute respiratory tract infection in Shanghai, 2013\u20132015. Front Microbiol 9:1836. https:\/\/doi.org\/10.3389\/fmicb.2018.01836","journal-title":"Front Microbiol"},{"key":"4480_CR17","doi-asserted-by":"publisher","first-page":"1961","DOI":"10.3389\/fimmu.2017.01961","volume":"8","author":"DP Cook","year":"2017","unstructured":"Cook DP, Gysemans C, Mathieu C (2017) Lactococcus lactis As a versatile vehicle for tolerogenic immunotherapy. Front Immunol 8:1961. https:\/\/doi.org\/10.3389\/fimmu.2017.01961","journal-title":"Front Immunol"},{"issue":"32","key":"4480_CR18","doi-asserted-by":"publisher","first-page":"3873","DOI":"10.1016\/j.vaccine.2015.06.068","volume":"33","author":"P Rees","year":"2015","unstructured":"Rees P, Edwards A, Powell C et al (2015) Pediatric immunization-related safety incidents in primary care: a mixed methods analysis of a national database. Vaccine 33(32):3873\u20133880. https:\/\/doi.org\/10.1016\/j.vaccine.2015.06.068","journal-title":"Vaccine"},{"issue":"793","key":"4480_CR19","doi-asserted-by":"publisher","first-page":"eadk3702","DOI":"10.1126\/scitranslmed.adk3702","volume":"17","author":"AS Rolig","year":"2025","unstructured":"Rolig AS, Peng X, Sturgill ER et al (2025) The response to anti-PD-1 and anti-LAG-3 checkpoint blockade is associated with regulatory T cell reprogramming. Sci Transl Med 17(793):eadk3702. https:\/\/doi.org\/10.1126\/scitranslmed.adk3702","journal-title":"Sci Transl Med"},{"issue":"1","key":"4480_CR20","doi-asserted-by":"publisher","first-page":"1222","DOI":"10.1186\/s12885-021-08974-3","volume":"21","author":"Y Sato","year":"2021","unstructured":"Sato Y, Fu Y, Liu H et al (2021) Tumor-immune profiling of CT-26 and Colon 26 syngeneic mouse models reveals mechanism of anti-PD-1 response. BMC Cancer 21(1):1222. https:\/\/doi.org\/10.1186\/s12885-021-08974-3","journal-title":"BMC Cancer"},{"issue":"3","key":"4480_CR21","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1016\/j.celrep.2017.09.081","volume":"21","author":"B Hiener","year":"2017","unstructured":"Hiener B, Horsburgh BA, Eden JS et al (2017) Identification of genetically intact HIV-1 proviruses in specific CD4(+) T Cells from effectively treated participants. Cell Rep 21(3):813\u2013822. https:\/\/doi.org\/10.1016\/j.celrep.2017.09.081","journal-title":"Cell Rep"},{"issue":"4","key":"4480_CR22","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1038\/ni.2829","volume":"15","author":"S Khare","year":"2014","unstructured":"Khare S, Ratsimandresy RA, de Almeida L et al (2014) The PYRIN domain-only protein POP3 inhibits ALR inflammasomes and regulates responses to infection with DNA viruses. Nat Immunol 15(4):343\u2013353. https:\/\/doi.org\/10.1038\/ni.2829","journal-title":"Nat Immunol"},{"issue":"7","key":"4480_CR23","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1038\/s41590-020-0651-3","volume":"21","author":"FR Carbone","year":"2020","unstructured":"Carbone FR (2020) Immovable memories: the journey to permanent residency. Nat Immunol 21(7):698\u2013699. https:\/\/doi.org\/10.1038\/s41590-020-0651-3","journal-title":"Nat Immunol"},{"issue":"5","key":"4480_CR24","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1038\/ni.3153","volume":"16","author":"CA Hunter","year":"2015","unstructured":"Hunter CA, Jones SA (2015) IL-6 as a keystone cytokine in health and disease. Nat Immunol 16(5):448\u2013457. https:\/\/doi.org\/10.1038\/ni.3153","journal-title":"Nat Immunol"},{"issue":"7","key":"4480_CR25","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1093\/annonc\/mdy155","volume":"29","author":"GN Hortobagyi","year":"2018","unstructured":"Hortobagyi GN, Stemmer SM, Burris HA et al (2018) Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer. Ann Oncol 29(7):1541\u20131547. https:\/\/doi.org\/10.1093\/annonc\/mdy155","journal-title":"Ann Oncol"},{"issue":"6529","key":"4480_CR26","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1126\/science.abf3363","volume":"371","author":"D Davar","year":"2021","unstructured":"Davar D, Dzutsev AK, McCulloch JA et al (2021) Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients. Science 371(6529):595\u2013602. https:\/\/doi.org\/10.1126\/science.abf3363","journal-title":"Science"},{"key":"4480_CR27","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1038\/s41423-024-01238-7","volume":"22","author":"M Perez-Penco","year":"2025","unstructured":"Perez-Penco M, Byrdal M, Lara de la Torre L et al (2025) The antitumor activity of TGF\u03b2-specific T cells is dependent on IL-6 signaling. Cell Mol Immunol 22:111\u2013126. https:\/\/doi.org\/10.1038\/s41423-024-01238-7","journal-title":"Cell Mol Immunol"},{"issue":"1","key":"4480_CR28","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.smim.2014.01.008","volume":"26","author":"DT Fisher","year":"2014","unstructured":"Fisher DT, Appenheimer MM, Evans SS (2014) The two faces of IL-6 in the tumor microenvironment. Semin Immunol 26(1):38\u201347. https:\/\/doi.org\/10.1016\/j.smim.2014.01.008","journal-title":"Semin Immunol"}],"container-title":["Cancer Immunology, Immunotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00262-026-04480-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00262-026-04480-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00262-026-04480-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T01:49:00Z","timestamp":1789609740000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00262-026-04480-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,30]]},"references-count":28,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["4480"],"URL":"https:\/\/doi.org\/10.1007\/s00262-026-04480-2","relation":{},"ISSN":["1432-0851"],"issn-type":[{"value":"1432-0851","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,30]]},"assertion":[{"value":"20 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number R44CA261509. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Miaki Fukuhara, Gary R. Fanger, and Christian Furlan Freguia are employees of Rise Therapeutics. Rise Therapeutics holds intellectual property related to the engineered probiotic described in this study. The remaining authors declare no competing interest.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All animal studies were conducted in accordance with institutional guidelines and were approved by the appropriate Institutional Animal Care and Use Committee (IACUC).","order":2,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"229"}}