{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T10:22:09Z","timestamp":1783074129249,"version":"3.54.6"},"reference-count":43,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004000","name":"Guangzhou Municipal Science and Technology Program key projects","doi-asserted-by":"publisher","award":["2024A04J4317"],"award-info":[{"award-number":["2024A04J4317"]}],"id":[{"id":"10.13039\/501100004000","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2023A1515030013"],"award-info":[{"award-number":["2023A1515030013"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2023A1515012981"],"award-info":[{"award-number":["2023A1515012981"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273305"],"award-info":[{"award-number":["82273305"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272790"],"award-info":[{"award-number":["82272790"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Pharmacological Research"],"published-print":{"date-parts":[[2026,7]]},"DOI":"10.1016\/j.phrs.2026.108209","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T16:26:41Z","timestamp":1778084801000},"page":"108209","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Blockade of the CLCF1\u2013CNTFR axis enhances the efficacy of GPC3 CAR-T cell therapy in hepatocellular carcinoma"],"prefix":"10.1016","volume":"229","author":[{"given":"Hao","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuzhong","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoran","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingzi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qijing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaopin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1268-3967","authenticated-orcid":false,"given":"Jianchuan","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"6","key":"10.1016\/j.phrs.2026.108209_bib1","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1016\/j.jhep.2022.08.021","article-title":"Global burden of primary liver cancer in 2020 and predictions to 2040","volume":"77","author":"RUMGAY","year":"2022","journal-title":"J. Hepatol."},{"issue":"4","key":"10.1016\/j.phrs.2026.108209_bib2","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/S2468-1253(24)00434-5","article-title":"Precision surgery for hepatocellular carcinoma","volume":"10","author":"MAGYAR","year":"2025","journal-title":"Lancet Gastroenterol. & Hepatol."},{"issue":"1","key":"10.1016\/j.phrs.2026.108209_bib3","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s13045-024-01549-2","article-title":"Immunosuppressive tumor microenvironment and immunotherapy of hepatocellular carcinoma: current status and prospectives","volume":"17","author":"SHEN","year":"2024","journal-title":"J. Hematol. & Oncol."},{"issue":"4","key":"10.1016\/j.phrs.2026.108209_bib4","doi-asserted-by":"crossref","DOI":"10.1002\/smmd.70023","article-title":"Integrating Single-Cell and Spatial Transcriptomics Reveals NK Cell Subpopulations Associated With Immunotherapy for Melanoma","volume":"4","author":"HU","year":"2025","journal-title":"Smart Med."},{"issue":"10","key":"10.1016\/j.phrs.2026.108209_bib5","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1038\/s41423-025-01308-4","article-title":"Immune microenvironment in hepatocellular carcinoma: from pathogenesis to immunotherapy","volume":"22","author":"SEYHAN","year":"2025","journal-title":"Cell. & Mol. Immunol."},{"key":"10.1016\/j.phrs.2026.108209_bib6","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.bmt.2023.04.002","article-title":"Integrin-based prognostic model predicts survival, immunotherapy response, and drug sensitivity in gastric cancer","volume":"5","author":"HU","year":"2024","journal-title":"Biomed. Technol."},{"issue":"1","key":"10.1016\/j.phrs.2026.108209_bib7","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s10555-024-10228-0","article-title":"CAR T-cell therapy for B-cell lymphomas: outcomes and resistance mechanisms","volume":"44","author":"KEARL","year":"2024","journal-title":"Cancer Metastas-.-. Rev."},{"key":"10.1016\/j.phrs.2026.108209_bib8","doi-asserted-by":"crossref","DOI":"10.1016\/j.pharmthera.2021.108007","article-title":"Chimeric antigen receptor (CAR) T-cell therapy for multiple myeloma","volume":"232","author":"CHOI","year":"2022","journal-title":"Pharmacol. & Ther."},{"issue":"4","key":"10.1016\/j.phrs.2026.108209_bib9","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.ccell.2025.03.019","article-title":"CAR-T therapy in solid tumors","volume":"43","author":"DU","year":"2025","journal-title":"Cancer Cell"},{"issue":"6","key":"10.1016\/j.phrs.2026.108209_bib10","first-page":"372","article-title":"Mechanisms of resistance to CAR T cell therapy","volume":"16","author":"SHAH","year":"2019","journal-title":"Nat. Rev. Clin. Oncol."},{"issue":"8047","key":"10.1016\/j.phrs.2026.108209_bib11","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1038\/s41586-024-08261-8","article-title":"Interleukin-15-armoured GPC3 CAR T cells for patients with solid cancers","volume":"637","author":"STEFFIN","year":"2025","journal-title":"Nature"},{"issue":"4","key":"10.1016\/j.phrs.2026.108209_bib12","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.ccell.2020.07.005","article-title":"Engineering CAR-T cells for next-generation cancer therapy","volume":"38","author":"HONG","year":"2020","journal-title":"Cancer Cell"},{"issue":"20","key":"10.1016\/j.phrs.2026.108209_bib13","doi-asserted-by":"crossref","first-page":"11458","DOI":"10.1073\/pnas.96.20.11458","article-title":"Novel neurotrophin-1\/B cell-stimulating factor-3: a cytokine of the IL-6 family","volume":"96","author":"SENALDI","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"5","key":"10.1016\/j.phrs.2026.108209_bib14","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.cytogfr.2015.07.014","article-title":"Cardiotrophin-like cytokine factor 1 (CLCF1) and neuropoietin (NP) signalling and their roles in development, adulthood, cancer and degenerative disorders","volume":"26","author":"SIMS","year":"2015","journal-title":"Cytokine & Growth Factor Rev."},{"issue":"25","key":"10.1016\/j.phrs.2026.108209_bib15","doi-asserted-by":"crossref","first-page":"22476","DOI":"10.1074\/jbc.M101681200","article-title":"Signaling pathways recruited by the cardiotrophin-like cytokine\/cytokine-like factor-1 composite cytokine: specific requirement of the membrane-bound form of ciliary neurotrophic factor receptor alpha component","volume":"276","author":"LELI\u00e8VRE","year":"2001","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.phrs.2026.108209_bib16","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.sbi.2016.07.012","article-title":"Engineering antibody therapeutics","volume":"38","author":"CHIU","year":"2016","journal-title":"Curr. Opin. Struct. Biol."},{"issue":"11","key":"10.1016\/j.phrs.2026.108209_bib17","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1038\/s41591-019-0612-2","article-title":"Antitumor activity of an engineered decoy receptor targeting CLCF1-CNTFR signaling in lung adenocarcinoma","volume":"25","author":"KIM","year":"2019","journal-title":"Nat. Med."},{"key":"10.1016\/j.phrs.2026.108209_bib18","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2025.107619","article-title":"The molecular receptor NKBB enhances the persistence and anti-hepatocellular carcinoma activity of GPC3 CAR-T cells","volume":"212","author":"SUI","year":"2025","journal-title":"Pharmacol. Res."},{"issue":"1","key":"10.1016\/j.phrs.2026.108209_bib19","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1186\/s12916-023-03016-0","article-title":"Targeted delivery of a PD-1-blocking scFv by CD133-specific CAR-T cells using nonviral Sleeping Beauty transposition shows enhanced antitumour efficacy for advanced hepatocellular carcinoma","volume":"21","author":"YANG","year":"2023","journal-title":"BMC Med."},{"issue":"5","key":"10.1016\/j.phrs.2026.108209_bib20","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1002\/hep.31792","article-title":"Cancer-Associated Fibroblast-Mediated Cellular Crosstalk Supports Hepatocellular Carcinoma Progression","volume":"73","author":"SONG","year":"2021","journal-title":"Hepatol. (Baltim. Md)"},{"issue":"11","key":"10.1016\/j.phrs.2026.108209_bib21","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1038\/s41571-023-00816-4","article-title":"Biomarkers for immunotherapy of hepatocellular carcinoma","volume":"20","author":"GRETEN","year":"2023","journal-title":"Nat. Rev. Clin. Oncol."},{"issue":"5","key":"10.1016\/j.phrs.2026.108209_bib22","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/j.jhep.2024.01.011","article-title":"Immunotherapy and transplantation for hepatocellular carcinoma","volume":"80","author":"TABRIZIAN","year":"2024","journal-title":"J. Hepatol."},{"issue":"6","key":"10.1016\/j.phrs.2026.108209_bib23","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.annonc.2024.03.005","article-title":"Nivolumab plus ipilimumab combination therapy in patients with advanced hepatocellular carcinoma previously treated with sorafenib: 5-year results from CheckMate 040","volume":"35","author":"MELERO","year":"2024","journal-title":"Ann. Oncol. Off. J. Eur. Soc. Med. Oncol."},{"issue":"4","key":"10.1016\/j.phrs.2026.108209_bib24","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1097\/HEP.0000000000000237","article-title":"Mechanisms of drug resistance in HCC","volume":"79","author":"LADD","year":"2024","journal-title":"Hepatol. (Baltim. Md)"},{"issue":"6745","key":"10.1016\/j.phrs.2026.108209_bib25","doi-asserted-by":"crossref","DOI":"10.1126\/science.adr3026","article-title":"Tumor-derived erythropoietin acts as an immunosuppressive switch in cancer immunity","volume":"388","author":"CHIU","year":"2025","journal-title":"Science (New York NY)"},{"key":"10.1016\/j.phrs.2026.108209_bib26","article-title":"The landscape of chimeric antigen receptor T cell therapy in breast cancer: Perspectives and outlook","volume":"13","author":"ZHANG","year":"2022","journal-title":"Front. Immunol."},{"issue":"3","key":"10.1016\/j.phrs.2026.108209_bib27","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/s41571-019-0297-y","article-title":"Engineering strategies to overcome the current roadblocks in CAR T cell therapy","volume":"17","author":"RAFIQ","year":"2020","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"10.1016\/j.phrs.2026.108209_bib28","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.cytogfr.2025.01.003","article-title":"Insights into IL-6\/JAK\/STAT3 signaling in the tumor microenvironment: Implications for cancer therapy","volume":"85","author":"THUYA","year":"2025","journal-title":"Cytokine & Growth Factor Rev."},{"issue":"2","key":"10.1016\/j.phrs.2026.108209_bib29","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.pharmthera.2013.09.004","article-title":"Targeting interleukin-6 in inflammatory autoimmune diseases and cancers","volume":"141","author":"YAO","year":"2014","journal-title":"Pharmacol. & Ther."},{"issue":"1","key":"10.1016\/j.phrs.2026.108209_bib30","first-page":"63","article-title":"IL6-STAT3-C\/EBP\u03b2-IL6 positive feedback loop in tumor-associated macrophages promotes the EMT and metastasis of lung adenocarcinoma","volume":"43","author":"HU","year":"2024","journal-title":"Journal experimental & clinical cancer research CR"},{"issue":"17","key":"10.1016\/j.phrs.2026.108209_bib31","doi-asserted-by":"crossref","DOI":"10.1002\/cam4.71179","article-title":"MCPIP1 Controls Hybrid EMT and Tumor Stemness via the IL6\/JAK2\/STAT3 Axis in Pancreatic Cancer","volume":"14","author":"DING","year":"2025","journal-title":"Cancer Med."},{"issue":"1","key":"10.1016\/j.phrs.2026.108209_bib32","article-title":"CD8(+) T cell-intrinsic IL-6 signaling promotes resistance to anti-PD-L1 immunotherapy","volume":"4","author":"HUSENI","year":"2023","journal-title":"Cell Rep. Med."},{"issue":"12","key":"10.1016\/j.phrs.2026.108209_bib33","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/s41577-018-0066-7","article-title":"Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer","volume":"18","author":"JONES","year":"2018","journal-title":"Nat. Rev. Immunol."},{"issue":"4","key":"10.1016\/j.phrs.2026.108209_bib34","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1038\/s41419-018-0458-4","article-title":"Cancer-associated fibroblasts induce PDL1+ neutrophils through the IL6-STAT3 pathway that foster immune suppression in hepatocellular carcinoma","volume":"9","author":"CHENG","year":"2018","journal-title":"Cell death & Dis."},{"issue":"25","key":"10.1016\/j.phrs.2026.108209_bib35","doi-asserted-by":"crossref","first-page":"14110","DOI":"10.1073\/pnas.1922729117","article-title":"Engineering a potent receptor superagonist or antagonist from a novel IL-6 family cytokine ligand","volume":"117","author":"KIM","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"2","key":"10.1016\/j.phrs.2026.108209_bib36","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1002\/med.21455","article-title":"Glypican-3: A promising biomarker for hepatocellular carcinoma diagnosis and treatment","volume":"38","author":"ZHOU","year":"2018","journal-title":"Med. Res. Rev."},{"key":"10.1016\/j.phrs.2026.108209_bib37","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2024.1489649","article-title":"CAR-T cell therapy for hepatocellular carcinoma: current trends and challenges","volume":"15","author":"ZHOU","year":"2024","journal-title":"Front. Immunol."},{"issue":"15","key":"10.1016\/j.phrs.2026.108209_bib38","doi-asserted-by":"crossref","first-page":"3979","DOI":"10.1158\/1078-0432.CCR-19-3259","article-title":"Chimeric Antigen Receptor-Glypican-3 T-Cell Therapy for Advanced Hepatocellular Carcinoma: Results of Phase I Trials","volume":"26","author":"SHI","year":"2020","journal-title":"Clinical cancer research official journal American Association Cancer Research"},{"issue":"9","key":"10.1016\/j.phrs.2026.108209_bib39","doi-asserted-by":"crossref","DOI":"10.3390\/cancers11091339","article-title":"Glypican 3-Targeted Therapy in Hepatocellular Carcinoma","volume":"11","author":"NISHIDA","year":"2019","journal-title":"Cancers"},{"issue":"1","key":"10.1016\/j.phrs.2026.108209_bib40","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1186\/s12943-024-02079-8","article-title":"Reshaping the tumor immune microenvironment to improve CAR-T cell-based cancer immunotherapy","volume":"23","author":"XIA","year":"2024","journal-title":"Mol. Cancer"},{"issue":"1","key":"10.1016\/j.phrs.2026.108209_bib41","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/s13045-021-01128-9","article-title":"IL-7 and CCL19-secreting CAR-T cell therapy for tumors with positive glypican-3 or mesothelin","volume":"14","author":"PANG","year":"2021","journal-title":"J. Hematol. & Oncol."},{"issue":"3","key":"10.1016\/j.phrs.2026.108209_bib42","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/s41577-025-01229-3","article-title":"Microenvironmental regulation of solid tumour resistance to CAR T cell therapy","volume":"26","author":"LAMPLUGH","year":"2026","journal-title":"Nat. Rev. Immunol."},{"issue":"2","key":"10.1016\/j.phrs.2026.108209_bib43","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1016\/j.ymthe.2024.12.014","article-title":"Potentiating CAR-T cell function in the immunosuppressive tumor microenvironment by inverting the TGF-\u03b2 signal","volume":"33","author":"ZHENG","year":"2025","journal-title":"Molecular therapy journal American Society Gene Therapy"}],"container-title":["Pharmacological Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1043661826001246?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1043661826001246?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T10:04:00Z","timestamp":1783073040000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1043661826001246"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":43,"alternative-id":["S1043661826001246"],"URL":"https:\/\/doi.org\/10.1016\/j.phrs.2026.108209","relation":{},"ISSN":["1043-6618"],"issn-type":[{"value":"1043-6618","type":"print"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Blockade of the CLCF1\u2013CNTFR axis enhances the efficacy of GPC3 CAR-T cell therapy in hepatocellular carcinoma","name":"articletitle","label":"Article Title"},{"value":"Pharmacological Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phrs.2026.108209","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"108209"}}