{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T15:40:00Z","timestamp":1792510800891,"version":"4.5.0"},"reference-count":35,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"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":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    This study investigated how tumor\u2010associated mast cells (TAMCs) contribute to immunosuppression and anti\u2010PD\u20101 resistance in hepatocellular carcinoma (HCC). TAMC infiltration as well as the levels of stem cell factor (SCF) and various chemokines were measured in clinical specimens obtained from 59 HCC patients. The recruitment and maintenance of TAMCs by HCC\u2010conditioned medium were examined, with a focus on the role of SCF in these processes. In addition, the chemotactic effect of CCL17 (secreted by activated TAMCs) on CCR4\u2010expressing regulatory T cells (Tregs) was evaluated. The functional impact of the recruited Tregs was further assessed by examining their capacity to inhibit the proliferation of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells and to suppress the secretion of cytotoxic effector molecules.\n                    <jats:italic>In vivo<\/jats:italic>\n                    experiments were also conducted to evaluate the antitumor efficacy of combining anti\u2010PD\u20101 antibodies with either cromolyn sodium or CCR4 antagonists. Analysis of HCC specimens revealed a marked accumulation of TAMCs, and the extent of TAMC infiltration was found to be positively correlated with both SCF and CCL17 levels. HCC cells were shown to actively recruit TAMCs and promote their proliferation through the secretion of SCF. Upon activation, TAMCs released CCL17, which potently chemotaxed Tregs in a CCR4\u2010dependent manner and subsequently suppressed the antitumor activity of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells.\n                    <jats:italic>In vivo<\/jats:italic>\n                    , the combination of anti\u2010PD\u20101 antibodies with cromolyn sodium or CCR4 antagonists yielded a synergistic antitumor effect, outperforming each agent used as monotherapy. Overall, these findings suggest that TAMCs drive immune suppression and confer resistance to anti\u2010PD\u20101 therapy in HCC through CCL17\/CCR4\u2010mediated Treg recruitment.\n                  <\/jats:p>","DOI":"10.1002\/jbt.71127","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T14:51:04Z","timestamp":1792507864000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tumor\u2010Associated Mast Cells Drive Immunosuppression and Resistance to Anti\u2010PD\u20101 Therapy in Hepatocellular Carcinoma Through CCL17\/CCR4\u2010mediated Regulatory T\u2010Cell Recruitment"],"prefix":"10.1002","volume":"40","author":[{"given":"Shuai","family":"Yang","sequence":"first","affiliation":[{"name":"Key Laboratory of Myocardial Ischemia, Ministry of Education The Second Affiliated Hospital of Harbin Medical University Harbin City Heilongjiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7771-748X","authenticated-orcid":false,"given":"Chuang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of General Surgery The Second Affiliated Hospital of Harbin Medical University Harbin City Heilongjiang Province 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