{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T17:54:35Z","timestamp":1782755675121,"version":"3.54.5"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T00:00:00Z","timestamp":1665619200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T00:00:00Z","timestamp":1676592000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims:<\/jats:title>\n            <jats:p>Chronic HBV infection is the leading cause of HCC and a serious health problem in China, East Asia, and North African countries. Effective treatment of HBV\u2010related HCC is currently unavailable. This study evaluated the therapeutic potential of T\u2010cell immunoreceptor with Ig and ITIM domains (TIGIT) blockade in HBV\u2010related HCC.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results:<\/jats:title>\n            <jats:p>A mouse model of spontaneous HBV\u2010related HCC was generated by replacing wild\u2010type hepatocytes with HBsAg<jats:sup>+<\/jats:sup> hepatocytes (namely HBs\u2010HepR mice). The tumors in HBs\u2010HepR mice were inflammation\u2010associated HCC, similar to HBV\u2010related HCC in patients, which was distinguished from other HCC mouse models, such as diethylnitrosamine\u2010induced HCC, TGF\u2010\u03b2\u2010activated kinase 1 knockout\u2013induced HCC, HCC in a stelic animal model, or NASH\u2010induced HCC. HCC in HBs\u2010HepR mice was characterized by an increased number of CD8<jats:sup>+<\/jats:sup> T cells, whereas the production of IL\u20102, TNF\u2010\u03b1, and interferon\u2010gamma (IFN\u2010\u03b3) by intrahepatic CD8<jats:sup>+<\/jats:sup> T cells was decreased. Increased expression of TIGIT on CD8<jats:sup>+<\/jats:sup> T cells was responsible for functional exhaustion. The therapeutic effect of TIGIT blockade was investigated at the early and middle stages of HCC progression in HBs\u2010HepR mice. TIGIT blockade reinvigorated intrahepatic CD8<jats:sup>+<\/jats:sup> T cells with increased TNF\u2010\u03b1 and IFN\u2010\u03b3 production and an increased number of CD8<jats:sup>+<\/jats:sup> T cells in tumors, thereby slowing the development of HCC in HBs\u2010HepR mice. Blocking PD\u2010L1 did not show direct therapeutic effects or synergize with TIGIT blockade.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Blockade of TIGIT alone enhanced the antitumor activity of CD8<jats:sup>+<\/jats:sup> T cells during the progression of HBV\u2010related HCC in a spontaneous HCC mouse model.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.32715","type":"journal-article","created":{"date-parts":[[2022,8,8]],"date-time":"2022-08-08T04:24:51Z","timestamp":1659932691000},"page":"965-981","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":33,"title":["Blockade of T\u2010cell receptor with Ig and ITIM domains elicits potent antitumor immunity in naturally occurring HBV\u2010related HCC in mice"],"prefix":"10.1097","volume":"77","author":[{"given":"Yuwei","family":"Wu","sequence":"first","affiliation":[{"name":"The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China"},{"name":"Institute of Immunology, University of Science and Technology of China, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolei","family":"Hao","sequence":"additional","affiliation":[{"name":"The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China"},{"name":"Institute of Immunology, University of Science and Technology of China, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiming","family":"Wei","sequence":"additional","affiliation":[{"name":"The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China"},{"name":"Institute of Immunology, University of Science and Technology of China, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Sun","sequence":"additional","affiliation":[{"name":"The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China"},{"name":"Institute of Immunology, University of Science and Technology of China, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongyan","family":"Chen","sequence":"additional","affiliation":[{"name":"The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China"},{"name":"Institute of Immunology, University of Science and Technology of China, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigang","family":"Tian","sequence":"additional","affiliation":[{"name":"The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China"},{"name":"Institute of Immunology, University of Science and Technology of China, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2023,2,17]]},"reference":[{"key":"hep32715-bib-0001-20250824","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/s41590-018-0044-z","article-title":"The immunology of hepatocellular carcinoma","volume":"19","year":"2018","journal-title":"Nat Immunol"},{"key":"hep32715-bib-0002-20250824","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1016\/S0140-6736(18)30010-2","article-title":"Hepatocellular 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