{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T16:05:10Z","timestamp":1784217910994,"version":"3.55.0"},"reference-count":47,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"unspecified","delay-in-days":15,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Guangdong Basic and Applied Basic Research Foundation","doi-asserted-by":"crossref","award":["2023A1515110285"],"award-info":[{"award-number":["2023A1515110285"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81972941"],"award-info":[{"award-number":["81972941"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82404119"],"award-info":[{"award-number":["82404119"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,6,26]]},"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Gut microbiota can modulate cancer immunotherapy and enhance the efficacy of programmed cell death protein 1 (PD-1) blockade in tumors, yet the responsible microbes and underlying mechanisms remain incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Publicly available anti-PD-1-treated melanoma microbiome cohorts were reanalyzed. Causal validation was performed using oral\n                      <jats:italic>Blautia coccoides<\/jats:italic>\n                      (\n                      <jats:italic>B. coccoides<\/jats:italic>\n                      ) supplementation in B16-F10 melanoma-bearing mice. Untargeted and targeted liquid chromatography-tandem mass spectrometry-based metabolomics, CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cell depletion, receptor identification and binding analyses, and downstream transcriptomic and biochemical assays were used to identify the key metabolite and investigate its mechanism of action.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified\n                      <jats:italic>Blautia<\/jats:italic>\n                      as enriched in melanoma patients responding to immune checkpoint inhibitors, with higher abundance associated with non-progression. In melanoma-bearing mice, oral\n                      <jats:italic>B. coccoides<\/jats:italic>\n                      suppressed tumor growth and increased intratumoral effector CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells. Metabolomic profiling identified acetate as a prominent\n                      <jats:italic>B. coccoides<\/jats:italic>\n                      -associated metabolite. Acetate enhanced CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cell effector function. CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cell depletion largely abrogated the antitumor effects of both\n                      <jats:italic>B. coccoides<\/jats:italic>\n                      and acetate, supporting a central role for CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells. Mechanistically, these findings support a model in which acetate is associated with a TLR3-linked signaling pathway in CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, accompanied by PI3K\/Akt activation and enhanced effector function. Notably,\n                      <jats:italic>B. coccoides<\/jats:italic>\n                      or acetate potentiated anti-PD-1 therapy in mouse melanoma models, supporting their potential as adjunctive strategies for melanoma immunotherapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These findings support a model of an acetate-TLR3-linked PI3K\/Akt signaling axis linking microbiota-associated metabolites to CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell-mediated antitumor immunity. Importantly, our study highlights both\n                      <jats:italic>B. coccoides<\/jats:italic>\n                      and its derivative, acetate, as preclinical adjunctive candidates to potentiate anti-PD-1 efficacy in melanoma.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2026-015617","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T15:30:27Z","timestamp":1784215827000},"page":"e015617","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["<i>Blautia coccoides<\/i>\n                    -derived acetate potentiates anti-PD-1 immunotherapy in melanoma by activating cytotoxic CD8\n                    <sup>+<\/sup>\n                    T cells"],"prefix":"10.1136","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3907-4790","authenticated-orcid":false,"given":"Zhiwen","family":"Zhang","sequence":"first","affiliation":[{"name":"Hunan Key Laboratory of Medical Epigenomics & Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China"},{"name":"The First School of Clinical Medicine, Southern Medical University; 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