{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T13:08:18Z","timestamp":1783948098673,"version":"3.55.0"},"reference-count":45,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100012542","name":"Sichuan Provincial Science and Technology Support Program","doi-asserted-by":"publisher","award":["2022YFS0619"],"award-info":[{"award-number":["2022YFS0619"]}],"id":[{"id":"10.13039\/100012542","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Pathology - Research and Practice"],"published-print":{"date-parts":[[2025,7]]},"DOI":"10.1016\/j.prp.2025.155995","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T12:06:33Z","timestamp":1746533193000},"page":"155995","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"special_numbering":"C","title":["Asiaticoside enhances the anti-tumor effect of anti-PDL1 by regulating T cell activity through increasing LCK activity"],"prefix":"10.1016","volume":"271","author":[{"given":"Qingyi","family":"Ren","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxi","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhong","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"5","key":"10.1016\/j.prp.2025.155995_bib1","doi-asserted-by":"crossref","DOI":"10.3390\/cancers16050901","article-title":"Hepatocellular carcinoma: old and emerging therapeutic targets","volume":"16","author":"Pessino","year":"2024","journal-title":"Cancers"},{"issue":"1","key":"10.1016\/j.prp.2025.155995_bib2","doi-asserted-by":"crossref","DOI":"10.3892\/mmr.2024.13255","article-title":"Research progress in the metabolic reprogramming of hepatocellular carcinoma (review)","volume":"30","author":"Gao","year":"2024","journal-title":"Mol. Med. Rep."},{"issue":"2","key":"10.1016\/j.prp.2025.155995_bib3","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1097\/SLA.0000000000000236","article-title":"Hepatic resection associated with good survival for selected patients with intermediate and advanced-stage hepatocellular carcinoma","volume":"260","author":"Zhong","year":"2014","journal-title":"Ann. Surg."},{"key":"10.1016\/j.prp.2025.155995_bib4","article-title":"Hepatocellular carcinoma","volume":"2","author":"Llovet","year":"2016","journal-title":"Nat. Rev. Dis. Prim."},{"issue":"7","key":"10.1016\/j.prp.2025.155995_bib5","doi-asserted-by":"crossref","DOI":"10.3390\/cancers12071914","article-title":"Locoregional therapy approaches for hepatocellular carcinoma: recent advances and management strategies","volume":"12","author":"Makary","year":"2020","journal-title":"Cancers"},{"issue":"7","key":"10.1016\/j.prp.2025.155995_bib6","first-page":"398","article-title":"Advances and future directions in the treatment of hepatocellular carcinoma","volume":"13","author":"Gosalia","year":"2017","journal-title":"Gastroenterol. Hepatol."},{"issue":"6","key":"10.1016\/j.prp.2025.155995_bib7","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0131403","article-title":"PD-L1 and survival in solid tumors: a meta-analysis","volume":"10","author":"Wu","year":"2015","journal-title":"PLoS One"},{"issue":"3","key":"10.1016\/j.prp.2025.155995_bib8","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.jhep.2016.12.009","article-title":"Current progress in immunotherapy of hepatocellular carcinoma","volume":"66","author":"Sprinzl","year":"2017","journal-title":"J. Hepatol."},{"issue":"1","key":"10.1016\/j.prp.2025.155995_bib9","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1186\/s13046-018-0777-4","article-title":"Immune checkpoint therapy in liver cancer","volume":"37","author":"Xu","year":"2018","journal-title":"J. Exp. Clin. Cancer Res.: CR"},{"issue":"1","key":"10.1016\/j.prp.2025.155995_bib10","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1093\/intimm\/dxu095","article-title":"Therapeutic uses of anti-PD-1 and anti-PD-L1 antibodies","volume":"27","author":"Philips","year":"2015","journal-title":"Int. Immunol."},{"key":"10.1016\/j.prp.2025.155995_bib11","doi-asserted-by":"crossref","DOI":"10.1016\/j.trecan.2024.03.010","article-title":"Immunometabolism of CD8(+) T cell differentiation in cancer","author":"Shi","year":"2024","journal-title":"Trends Cancer"},{"issue":"9","key":"10.1016\/j.prp.2025.155995_bib12","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.it.2023.07.005","article-title":"Factors contributing to the potency of CD8(+) T cells","volume":"44","author":"Sykulev","year":"2023","journal-title":"Trends Immunol."},{"issue":"10","key":"10.1016\/j.prp.2025.155995_bib13","doi-asserted-by":"crossref","first-page":"4648","DOI":"10.4049\/jimmunol.1400120","article-title":"CD8+ T cells define an unexpected role in live-attenuated vaccine protective immunity against Chlamydia trachomatis infection in macaques","volume":"192","author":"Olivares-Zavaleta","year":"2014","journal-title":"J. Immunol. (Baltim. Md: 1950)"},{"issue":"1","key":"10.1016\/j.prp.2025.155995_bib14","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1111\/imr.13203","article-title":"T-cell heterogeneity, progenitor-progeny relationships, and function during latent and chronic viral infections","volume":"316","author":"Sandu","year":"2023","journal-title":"Immunol. Rev."},{"issue":"6055","key":"10.1016\/j.prp.2025.155995_bib15","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/319682a0","article-title":"Expression of a new tyrosine protein kinase is stimulated by retrovirus promoter insertion","volume":"319","author":"Voronova","year":"1986","journal-title":"Nature"},{"key":"10.1016\/j.prp.2025.155995_bib16","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1007\/s12195-016-0438-7","article-title":"Predictive model of lymphocyte-specific protein tyrosine kinase (LCK) autoregulation","volume":"9","author":"Rohrs","year":"2016","journal-title":"Cell. Mol. Bioeng."},{"issue":"5","key":"10.1016\/j.prp.2025.155995_bib17","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/j.immuni.2016.04.011","article-title":"A cholesterol-based allostery model of T cell receptor phosphorylation","volume":"44","author":"Swamy","year":"2016","journal-title":"Immunity"},{"key":"10.1016\/j.prp.2025.155995_bib18","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1146\/annurev.immunol.021908.132706","article-title":"T cell activation","volume":"27","author":"Smith-Garvin","year":"2009","journal-title":"Annu. Rev. Immunol."},{"issue":"2","key":"10.1016\/j.prp.2025.155995_bib19","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.tibs.2017.11.008","article-title":"TCR signaling: mechanisms of initiation and propagation","volume":"43","author":"Courtney","year":"2018","journal-title":"Trends Biochem. Sci."},{"key":"10.1016\/j.prp.2025.155995_bib20","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.csbj.2019.03.006","article-title":"Application of PD-1 blockade in cancer immunotherapy","volume":"17","author":"Wu","year":"2019","journal-title":"Comput. Struct. Biotechnol. J."},{"issue":"4","key":"10.1016\/j.prp.2025.155995_bib21","doi-asserted-by":"crossref","DOI":"10.3390\/biomedicines11041020","article-title":"Immune checkpoint inhibitors in hepatocellular carcinoma: current strategies and biomarkers predicting response and\/or resistance","volume":"11","author":"Pelizzaro","year":"2023","journal-title":"Biomedicines"},{"issue":"12","key":"10.1016\/j.prp.2025.155995_bib22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-018-0191-1","article-title":"Immune checkpoint inhibitors: recent progress and potential biomarkers","volume":"50","author":"Darvin","year":"2018","journal-title":"Exp. Mol. Med."},{"key":"10.1016\/j.prp.2025.155995_bib23","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.intimp.2017.09.026","article-title":"Quercetin protects mouse liver against triptolide-induced hepatic injury by restoring Th17\/Treg balance through Tim-3 and TLR4-MyD88-NF-\u03baB pathway","volume":"53","author":"Wei","year":"2017","journal-title":"Int. Immunopharmacol."},{"issue":"6","key":"10.1016\/j.prp.2025.155995_bib24","doi-asserted-by":"crossref","DOI":"10.1042\/BSR20180895","article-title":"Zhenbao pill reduces Treg cell proportion in acute spinal cord injury rats by regulating TUG1\/miR-214\/HSP27 axis","volume":"38","author":"He","year":"2018","journal-title":"Biosci. Rep."},{"issue":"2","key":"10.1016\/j.prp.2025.155995_bib25","doi-asserted-by":"crossref","first-page":"523","DOI":"10.5114\/aoms.2019.85349","article-title":"Salidroside regulates imbalance of Th17\/Treg and promotes ischemic tolerance by targeting STAT-3 in cerebral ischemia-reperfusion injury","volume":"17","author":"Yin","year":"2021","journal-title":"Arch. Med. Sci.: AMS"},{"issue":"7","key":"10.1016\/j.prp.2025.155995_bib26","doi-asserted-by":"crossref","DOI":"10.1016\/j.heliyon.2023.e17390","article-title":"Asiaticoside ameliorates renal ischemia\/reperfusion injury by promoting CD4(+)CD25(+)FOXP3(+) treg cell differentiation","volume":"9","author":"Tang","year":"2023","journal-title":"Heliyon"},{"key":"10.1016\/j.prp.2025.155995_bib27","doi-asserted-by":"crossref","DOI":"10.12659\/MSM.924435","article-title":"Asiaticoside antagonizes proliferation and chemotherapeutic drug resistance in hepatocellular carcinoma (HCC) cells","volume":"26","author":"Ma","year":"2020","journal-title":"Med. Sci. Monit.: Int. Med. J. Exp. Clin. Res."},{"issue":"4","key":"10.1016\/j.prp.2025.155995_bib28","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1158\/1078-0432.CCR-20-2571","article-title":"Camrelizumab in combination with apatinib in patients with advanced hepatocellular carcinoma (RESCUE): a nonrandomized, open-label, phase II trial","volume":"27","author":"Xu","year":"2021","journal-title":"Clin. Cancer Res.: Off. J. Am. Assoc. Cancer Res."},{"key":"10.1016\/j.prp.2025.155995_bib29","doi-asserted-by":"crossref","DOI":"10.1016\/j.ctrv.2020.102134","article-title":"Association between immune-related side effects and efficacy and benefit of immune checkpoint inhibitors \u2013 a systematic review and meta-analysis","volume":"92","author":"Hussaini","year":"2021","journal-title":"Cancer Treat. Rev."},{"issue":"19","key":"10.1016\/j.prp.2025.155995_bib30","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1200\/JCO.2016.71.6795","article-title":"Avelumab, an anti-programmed death-ligand 1 antibody, in patients with refractory metastatic urothelial carcinoma: results from a multicenter, phase Ib study","volume":"35","author":"Apolo","year":"2017","journal-title":"J. Clin. Oncol.: Off. J. Am. Soc. Clin. Oncol."},{"issue":"1","key":"10.1016\/j.prp.2025.155995_bib31","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1186\/s12885-019-5701-6","article-title":"Immune-related adverse events associated with programmed cell death protein-1 and programmed cell death ligand 1 inhibitors for non-small cell lung cancer: a PRISMA systematic review and meta-analysis","volume":"19","author":"Sun","year":"2019","journal-title":"BMC Cancer"},{"issue":"3","key":"10.1016\/j.prp.2025.155995_bib32","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.immuni.2018.03.014","article-title":"Regulation and function of the PD-L1 checkpoint","volume":"48","author":"Sun","year":"2018","journal-title":"Immunity"},{"issue":"18","key":"10.1016\/j.prp.2025.155995_bib33","first-page":"6860","article-title":"On the site and mode of antigen presentation for the initiation of clonal expansion of CD8 T cells specific for a natural tumor antigen","volume":"61","author":"Bai","year":"2001","journal-title":"Cancer Res."},{"key":"10.1016\/j.prp.2025.155995_bib34","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1111\/j.0105-2896.2006.00391.x","article-title":"CD8+ T-cell memory in tumor immunology and immunotherapy","volume":"211","author":"Klebanoff","year":"2006","journal-title":"Immunol. Rev."},{"issue":"3","key":"10.1016\/j.prp.2025.155995_bib35","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/ni889","article-title":"Lineage relationship and protective immunity of memory CD8 T cell subsets","volume":"4","author":"Wherry","year":"2003","journal-title":"Nat. Immunol."},{"issue":"6754","key":"10.1016\/j.prp.2025.155995_bib36","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1038\/44385","article-title":"Two subsets of memory T lymphocytes with distinct homing potentials and effector functions","volume":"401","author":"Sallusto","year":"1999","journal-title":"Nature"},{"key":"10.1016\/j.prp.2025.155995_bib37","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1146\/annurev.immunol.22.012703.104702","article-title":"Central memory and effector memory T cell subsets: function, generation, and maintenance","volume":"22","author":"Sallusto","year":"2004","journal-title":"Annu. Rev. Immunol."},{"issue":"17-18","key":"10.1016\/j.prp.2025.155995_bib38","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1016\/j.cca.2011.11.006","article-title":"Surface markers of lymphocyte activation and markers of cell proliferation","volume":"413","author":"Shipkova","year":"2012","journal-title":"Clin. Chim. Acta; Int. J. Clin. Chem."},{"issue":"4","key":"10.1016\/j.prp.2025.155995_bib39","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/s41577-021-00574-3","article-title":"CD8(+) T cell differentiation and dysfunction in cancer","volume":"22","author":"Philip","year":"2022","journal-title":"Nat. Rev. Immunol."},{"issue":"6","key":"10.1016\/j.prp.2025.155995_bib40","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1007\/s00005-014-0293-y","article-title":"Heterogeneity in the differentiation and function of CD8\u207a T cells","volume":"62","author":"Mittr\u00fccker","year":"2014","journal-title":"Arch. Immunol. et Ther. Exp."},{"issue":"14","key":"10.1016\/j.prp.2025.155995_bib41","doi-asserted-by":"crossref","DOI":"10.3390\/ijms241411471","article-title":"Immune system and hepatocellular carcinoma (HCC): new insights into HCC progression","volume":"24","author":"Kotsari","year":"2023","journal-title":"Int. J. Mol. Sci."},{"issue":"7","key":"10.1016\/j.prp.2025.155995_bib42","doi-asserted-by":"crossref","DOI":"10.3390\/cells11071164","article-title":"Interleukin-6 at the host-tumor interface: STAT3 in biomolecular condensates in cancer cells","volume":"11","author":"Sehgal","year":"2022","journal-title":"Cells"},{"issue":"10","key":"10.1016\/j.prp.2025.155995_bib43","doi-asserted-by":"crossref","DOI":"10.3390\/biomedicines11102623","article-title":"Interleukin-6 in hepatocellular carcinoma: a dualistic point of view","volume":"11","author":"Nenu","year":"2023","journal-title":"Biomedicines"},{"issue":"14","key":"10.1016\/j.prp.2025.155995_bib44","doi-asserted-by":"crossref","DOI":"10.3390\/ijms20143500","article-title":"Beyond TCR signaling: emerging functions of Lck in cancer and immunotherapy","volume":"20","author":"Bommhardt","year":"2019","journal-title":"Int. J. Mol. Sci."},{"issue":"8","key":"10.1016\/j.prp.2025.155995_bib45","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1038\/s41577-018-0020-8","article-title":"Regulatory mechanisms in T cell receptor signalling","volume":"18","author":"Gaud","year":"2018","journal-title":"Nat. Rev. Immunol."}],"container-title":["Pathology - Research and Practice"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0344033825001876?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0344033825001876?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T08:26:32Z","timestamp":1778747192000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0344033825001876"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":45,"alternative-id":["S0344033825001876"],"URL":"https:\/\/doi.org\/10.1016\/j.prp.2025.155995","relation":{},"ISSN":["0344-0338"],"issn-type":[{"value":"0344-0338","type":"print"}],"subject":[],"published":{"date-parts":[[2025,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Asiaticoside enhances the anti-tumor effect of anti-PDL1 by regulating T cell activity through increasing LCK activity","name":"articletitle","label":"Article Title"},{"value":"Pathology - Research and Practice","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.prp.2025.155995","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Published by Elsevier GmbH.","name":"copyright","label":"Copyright"}],"article-number":"155995"}}