{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T10:07:25Z","timestamp":1787998045819,"version":"build-2784847793"},"reference-count":79,"publisher":"American Association for Cancer Research (AACR)","issue":"1","funder":[{"name":"Mrs. Anneke Hoogendijk"},{"name":"Foundation Weteringschans"},{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["09150162210100"],"award-info":[{"award-number":["09150162210100"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021821","name":"Oncode Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100021821","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,1,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Studies have identified a link between specific microbiome-derived bacteria and immune checkpoint blockade (ICB) efficacy. However, these species lack consistency across studies, and their immunomodulatory mechanisms remain elusive. To understand the influence of the microbiome on ICB response, we studied its functional capacity. Using pan-cancer metagenomics data from ICB-treated patients, we showed that community-level metabolic pathways are stable across individuals, making them suitable for predicting ICB response. We identified several microbial metabolic processes significantly associated with response, including the methylerythritol 4-phosphate (MEP) pathway, which was associated with response and induced V\u03b42 T cell\u2013mediated antitumor responses in patient-derived tumor organoids. In contrast, riboflavin synthesis was associated with ICB resistance, and its intermediates induced mucosal-associated invariant T (MAIT) cell\u2013mediated immune suppression. Moreover, gut metabolomics revealed that high riboflavin levels were linked to worse survival in patients with abundant intratumoral MAIT cells. Collectively, our results highlight the relevance of metabolite-mediated microbiome\u2013immune cell cross-talk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>Microbial metabolic pathways are highly conserved across individuals and therefore offer an opportunity to link the microbiome to immunotherapy efficacy. We identified specific microbial metabolic pathways associated with response to ICB and provided mechanistic insights into the immunomodulatory influence of these pathways on antitumor immunity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/2159-8290.cd-24-1669","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T14:55:03Z","timestamp":1758812103000},"page":"95-113","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Microbial Metabolic Pathways Guide Response to Immune Checkpoint Blockade Therapy"],"prefix":"10.1158","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6177-8607","authenticated-orcid":false,"given":"Iris L.","family":"Mimpen","sequence":"first","affiliation":[{"name":"1Division of Molecular Oncology & Immunology, The Netherlands Cancer Institute, Amsterdam, the Netherlands."},{"name":"2Oncode Institute, The Netherlands Cancer Institute, 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