{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T11:49:01Z","timestamp":1792669741122,"version":"4.5.0"},"reference-count":51,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"unspecified","delay-in-days":26,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 111-2320-B-002-060-MY3"],"award-info":[{"award-number":["MOST 111-2320-B-002-060-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,3,2]]},"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The liver\u2019s inherently immunosuppressive microenvironment presents a major barrier to effective immunotherapy for hepatocellular carcinoma (HCC). Although interleukin-10 (IL-10) has demonstrated antitumor activity in several cancer models, its therapeutic potential in HCC remains unclear. Here, we investigated whether liver-directed delivery of IL-10 using an adeno-associated virus vector (AAV-IL-10) could enhance antitumor immunity in HCC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Syngeneic orthotopic and intrahepatic metastatic HCC mouse models were used to evaluate the effects of liver-directed AAV-IL-10 therapy. Tumor burden, immune cell infiltration, and functional activation were assessed by flow cytometry and related analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Liver-directed AAV-IL-10 treatment significantly reduced intrahepatic tumor burden and promoted robust infiltration of CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells into the tumor microenvironment. AAV-IL-10 enhanced the functional activation of natural killer cells and CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, as reflected by increased expression of effector cytokines and cytotoxic molecules. Notably, AAV-IL-10 augmented the effector capacity of terminally exhausted CD8\n                      <jats:sup>+<\/jats:sup>\n                      tumor-infiltrating lymphocytes and expanded a population of CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells with a tissue-resident memory (Trm)-like phenotype. These Trm-like CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells were liver-resident and persisted after tumor clearance. Importantly, the antitumor effects of AAV-IL-10 were confined to the liver and did not affect the growth of distant subcutaneous tumors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Liver-directed AAV-IL-10 delivery overcomes local immunosuppression and enhances CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell-mediated antitumor immunity in murine HCC models. These findings support targeted IL-10 delivery as a promising strategy to improve immunotherapy outcomes in liver cancer.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-012460","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T15:50:12Z","timestamp":1774626612000},"page":"e012460","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Liver-directed AAV-IL-10 therapy enhances CD8\n                    <sup>+<\/sup>\n                    T cell-mediated immunity against hepatocellular carcinoma"],"prefix":"10.1136","volume":"14","author":[{"given":"Chia-I","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, 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