{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T02:53:20Z","timestamp":1790996000496,"version":"4.1.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    The link between the intestinal microflora and cancer outcomes has been recognized for over a decade. Several recent studies have demonstrated that the gut microbiome is associated with the efficiency of T-cell checkpoint blockade therapy for cancer, raising interest in strategies to harness this effect via consumption of live microorganisms (probiotics). The probiotic\n                    <jats:italic>Clostridium butyricum<\/jats:italic>\n                    strain MIYAIRI 588 (CBM588) improves response rates and overall survival in patients receiving immune checkpoint inhibitor (ICI) therapy for non-small cell lung cancer and metastatic renal cell carcinoma but the mechanism underlying this benefit remains unclear. Here, we show that CBM588 spores induce a population of V\u03b39V\u03b42 T-cells from the peripheral blood of healthy donors and lung cancer patients. A subset of these T-cells responded to, and directly lysed, cancer cell lines via a butyrophilin 3A-dependent mechanism. In patients taking CBM588 alongside checkpoint blockade, using samples from a cohort of 38 patients, peripheral blood V\u03b42\n                    <jats:sup>+<\/jats:sup>\n                    T-cells expressed the activation marker CD69 more frequently than in those receiving checkpoint blockade alone and the frequency of V\u03b42\n                    <jats:sup>+<\/jats:sup>\n                    CD69\n                    <jats:sup>+<\/jats:sup>\n                    cells increased following initiation of CBM588 treatment (p = 0.0041). Pleural effusions from patients receiving ICI with CBM588, although available from only three individuals, also showed a notable shift in the local \u03b3\u03b4 T-cell compartment from the expected V\u03b41 dominance towards V\u03b42 cells, suggesting altered recruitment or retention of V\u03b42 cells at the tumour site. Across the patient cohort, higher post-treatment frequencies of CD69\n                    <jats:sup>+<\/jats:sup>\n                    V\u03b42 T-cells were associated with improved survival and more favourable clinical outcomes. These findings provide a potential mechanism by which manipulation of the intestinal microflora might contribute to cancer prognosis through effects on immune effector cells with intrinsic anticancer properties.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1750569","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T05:51:03Z","timestamp":1775022663000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["A probiotic bacterium modulates antitumour \u03b3\u03b4 T-cell responses in lung cancer"],"prefix":"10.3389","volume":"17","author":[{"given":"Yoshihiko","family":"Goto","sequence":"first","affiliation":[{"name":"Division of Infection and Immunity, Joint Research Center for Human Retrovirus Infection, Kumamoto University","place":["Kumamoto, Japan"]},{"name":"Department of Respiratory Medicine, Faculty of Life Sciences, Kumamoto University","place":["Kumamoto, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garry","family":"Dolton","sequence":"additional","affiliation":[{"name":"Division of Infection and immunity Cardiff University School of Medicine","place":["Cardiff, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Thomas","sequence":"additional","affiliation":[{"name":"Division of Infection and immunity Cardiff University School of Medicine","place":["Cardiff, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Th\u00e9o","family":"Morin","sequence":"additional","affiliation":[{"name":"Division of Infection and immunity Cardiff University School of Medicine","place":["Cardiff, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Tajima","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, Joint Research Center for Human Retrovirus Infection, Kumamoto University","place":["Kumamoto, Japan"]},{"name":"Department of Respiratory Medicine, Faculty of Life Sciences, Kumamoto University","place":["Kumamoto, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Imamura","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Faculty of Life Sciences, Kumamoto University","place":["Kumamoto, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Sakata","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Faculty of Life Sciences, Kumamoto University","place":["Kumamoto, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Oka","sequence":"additional","affiliation":[{"name":"R&D Division, Miyarisan Pharmaceutical Co., Ltd.","place":["Saitama, 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Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Tomita","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Faculty of Life Sciences, Kumamoto University","place":["Kumamoto, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew K.","family":"Sewell","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, Joint Research Center for Human Retrovirus Infection, Kumamoto University","place":["Kumamoto, Japan"]},{"name":"Division of Infection and immunity Cardiff University School of Medicine","place":["Cardiff, United Kingdom"]},{"name":"Systems Immunity Research Institute, Cardiff University","place":["Cardiff, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chihiro","family":"Motozono","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, Joint Research Center for Human Retrovirus Infection, Kumamoto 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