{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:43:36Z","timestamp":1791845016890,"version":"4.3.4"},"reference-count":61,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2020QH068"],"award-info":[{"award-number":["ZR2020QH068"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2021MH049"],"award-info":[{"award-number":["ZR2021MH049"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2025MS1312"],"award-info":[{"award-number":["ZR2025MS1312"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2025MS1429"],"award-info":[{"award-number":["ZR2025MS1429"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The limited clinical efficacy of immune checkpoint inhibitors (ICIs) remains a major challenge in the treatment of bladder cancer (BCa). Here, we report that a ketogenic diet (KD) and its principal circulating metabolite, \u03b2\u2010hydroxybutyrate (\u03b2\u2010HB), suppress bladder tumor growth and enhance responses to PD\u2010L1 inhibitor. In a syngeneic MB49 model, KD reduced tumor growth compared with normal diet (ND). KD increased plasma \u03b2\u2010HB and was associated with higher intratumoral PD\u2010L1 expression. Exogenous \u03b2\u2010HB supplementation under ND recapitulated the antitumor effect of KD, further enhancing anti\u2010PD\u2010L1 efficacy. Mechanistically, \u03b2\u2010HB increased intracellular reactive oxygen species (ROS) and disrupted mitochondrial membrane potential in bladder cancer cells, leading to ATP depletion and enhanced apoptosis. Besides, \u03b2\u2010HB also upregulated PD\u2010L1 in\u00a0vitro and in\u00a0vivo through GPR109A\u2010JAK2\u2010STAT3 signaling axis. Immune profiling of treated tumors showed increased infiltration and effector function of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells and NK cells and decreased immunosuppressive populations, changes that were further amplified when combined with anti\u2010PD\u2010L1. Together, our results indicate that KD and \u03b2\u2010HB exert both tumor intrinsic and immune modulatory effects that sensitize bladder tumors to PD\u2010L1 inhibitor, supporting further evaluation of ketogenic interventions as adjuvants to immunotherapy in BCa.\n                  <\/jats:p>","DOI":"10.1111\/cas.70447","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T11:31:46Z","timestamp":1781177506000},"page":"2379-2396","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ketogenic Diet and \u03b2\u2010Hydroxybutyrate Suppress Bladder Cancer Growth and Enhance Anti\u2010\n                    <scp>PD<\/scp>\n                    \u2010\n                    <scp>L1<\/scp>\n                    Immunotherapy Efficacy"],"prefix":"10.1111","volume":"117","author":[{"given":"Yuan","family":"Zeng","sequence":"first","affiliation":[{"name":"Department of Urology, Qilu Hospital, Cheeloo College of Medicine Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gangli","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Urology, Qilu Hospital, Cheeloo College of Medicine Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Urology, Qilu Hospital, Cheeloo College of Medicine Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bohao","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Xiongan Xuanwu Hospital  Xiongan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haochen","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Urology, Qilu Hospital, Cheeloo College of Medicine Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Urology, Qilu Hospital, Cheeloo College of Medicine Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5961-710X","authenticated-orcid":false,"given":"Zhao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Urology, Qilu Hospital, Cheeloo College of Medicine Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,11]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2019.08.016"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2016.06.010"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2017.01.002"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.109821"},{"issue":"2","key":"e_1_2_13_7_1","article-title":"Immune\u2010Checkpoint Inhibitors in Advanced Bladder Cancer: Seize the Day","volume":"10","author":"Maiorano B. 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