{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T08:53:30Z","timestamp":1790931210163,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Indole\u20103\u2010propionic acid (IPA) is documented to improve the effectiveness of tumor immunotherapy via regulating anti\u2010tumor immunity. However, the impacts of IPA in hepatocellular carcinoma (HCC) patients undergoing sintilimab combined with bevacizumab (SCB) treatment remain unknown. This study investigated the effects and underlying mechanisms of IPA in SCB\u2010treated HCC. Serum, tumor tissue, fecal and lymph node tissue samples were collected from HCC patients with or without a response to SCB therapy. Humanized orthotopic and subcutaneous HCC NOG mouse models were established. IPA\u2010treated mouse dendritic cells (DCs) were co\u2010cultured with mouse CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cells, which were subsequently co\u2010cultured with Hepa1\u20106 cells. IPA levels were elevated in the serum, tumor tissues, and feces of responders, and serum IPA levels were positively correlated with the proportion of IFN\u2010\u03b3\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in tumor tissues as well asac\u2010H3K27 and IL\u201012A levels in lymph node DCs. IPA amplified the suppressive impact of SCB on tumor growth in HCC mice. Moreover, IPA increased ac\u2010H3K27 and IL\u201012A levels in DCs and upregulated effector CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell immunity in HCC mice. Administration of a CD8\u2010neutralizing antibody and injection of shIL\u201012A\u2010transfected DCs weakened IPA\u2010mediated inhibition of HCC in\u00a0vivo. Furthermore, the ac\u2010H3K27 inhibitor A\u2010485 suppressed IL\u201012A expression and effector CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell immunity induced by IPA, thereby promoting the proliferation, invasion, and migration of Hepa1\u20106 cells in\u00a0vitro. These findings demonstrate that IPA enhances the effect of SCB\u2010treated HCC by upregulating H3K27 acetylation to promote IL\u201012A expression in DCs, thereby potentiating CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell immunity, which provides a basis for its potential use as a clinical adjuvant therapy.\n                  <\/jats:p>","DOI":"10.1111\/cas.70462","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T14:52:10Z","timestamp":1784213530000},"page":"2705-2718","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Indole\u20103\u2010Propionic Acid Drives Dendritic\n                    <scp>H3K27<\/scp>\n                    Acetylation to Enhance\n                    <scp>CD8<\/scp>\n                    + T Cell Immunity in Hepatocellular Carcinoma"],"prefix":"10.1111","volume":"117","author":[{"given":"Rui","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary Pancreatic Medicine and Interventional Medicine Second Hospital of Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Pancreatic Medicine and Interventional Medicine Second Hospital of Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Pancreatic Medicine and Interventional Medicine Second Hospital of Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenrui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Pancreatic Medicine and Interventional Medicine Second Hospital of Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanlan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Pancreatic Medicine and Interventional Medicine Second Hospital of Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Pancreatic Medicine and Interventional Medicine Second Hospital of Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengnan","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Pancreatic Medicine and Interventional Medicine Second Hospital of Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6210-4526","authenticated-orcid":false,"given":"Zhenjing","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Pancreatic Medicine and Interventional Medicine Second Hospital of Jilin University  Changchun 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