{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T20:00:14Z","timestamp":1770840014544,"version":"3.50.1"},"reference-count":29,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T00:00:00Z","timestamp":1731456000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005762","name":"National Taiwan University Hospital","doi-asserted-by":"publisher","award":["112\u2010BIH007"],"award-info":[{"award-number":["112\u2010BIH007"]}],"id":[{"id":"10.13039\/501100005762","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Hepato Biliary Pancreat"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Immune checkpoint inhibitors are effective to treat hepatocellular carcinoma (HCC) yet only successful in a small part of patients. This study aimed to investigate whether poly\u2010ICLC, an immune stimulant, can enhance the antitumor effects of anti\u2010PD\u20101 on mouse HCC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We established two syngeneic HCC mouse models with BNL cells in BALB\/c mice and Hep\u201055.1 C cells in C57BL\/6\u2009J mice. Mice with subcutaneous HCC tumors received one of five treatments: control, anti\u2010PD\u20101, intratumoral (IT) poly\u2010ICLC, anti\u2010PD\u20101 plus intramuscular (IM) poly\u2010ICLC, or anti\u2010PD\u20101 plus IT poly\u2010ICLC. Tumor volumes were measured, CD8+ T lymphocytes in tumors and spleen were analyzed, and interferon\u2010\u03b3 activity was assessed by ELISpot. Immune cell types and abundance were evaluated with NanoString nCounter IO360 panels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Cotreatment with poly\u2010ICLC significantly enhanced the antitumor effects of anti\u2010PD\u20101, with IT administration being more effective than IM. IT poly\u2010ICLC also induced more significant CD8<jats:sup>+<\/jats:sup> T cell infiltration and interferon\u2010\u03b3 activity in the tumor and spleen, and more upregulation of both interferon\u2010\u03b3 and M1 macrophage signals in the tumor microenvironment while downregulating several cancer\u2010promoting pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Combination therapy with poly\u2010ICLC, especially through IT route, and anti\u2010PD\u20101 provides significantly greater antitumor effects than anti\u2010PD\u20101 monotherapy in syngeneic mouse models of HCC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jhbp.12088","type":"journal-article","created":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T05:09:01Z","timestamp":1731560941000},"page":"139-150","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Intratumoral administration of poly\u2010<scp>ICLC<\/scp> enhances the antitumor effects of anti\u2010<scp>PD<\/scp>\u20101"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3120-6848","authenticated-orcid":false,"given":"Shin\u2010Yun","family":"Liu","sequence":"first","affiliation":[{"name":"Liver Disease Prevention and Treatment Research Foundation  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chia\u2010Lang","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Medical Research National Taiwan University Hospital  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shih\u2010Feng","family":"Yang","sequence":"additional","affiliation":[{"name":"Liver Disease Prevention and Treatment Research Foundation  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsuan\u2010Shu","family":"Lee","sequence":"additional","affiliation":[{"name":"Liver Disease Prevention and Treatment Research Foundation  Taipei 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