{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T03:23:15Z","timestamp":1793848995184,"version":"4.6.1"},"reference-count":48,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Phytomedicine"],"published-print":{"date-parts":[[2024,1]]},"DOI":"10.1016\/j.phymed.2023.155191","type":"journal-article","created":{"date-parts":[[2023,11,5]],"date-time":"2023-11-05T10:28:53Z","timestamp":1699180133000},"page":"155191","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":25,"special_numbering":"C","title":["Tanshinone IIA normalized hepatocellular carcinoma vessels and enhanced PD-1 inhibitor efficacy by inhibiting ELTD1"],"prefix":"10.1016","volume":"123","author":[{"given":"Dengxuan","family":"Mao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Che","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaoying","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4691-4348","authenticated-orcid":false,"given":"Yuping","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiege","family":"Huo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.phymed.2023.155191_bib0001","doi-asserted-by":"crossref","DOI":"10.1016\/j.pharmthera.2021.107986","article-title":"Modulating tumor-associated macrophages to enhance the efficacy of immune checkpoint inhibitors: a TAM-pting approach","volume":"231","author":"Chamseddine","year":"2022","journal-title":"Pharmacol. Ther."},{"key":"10.1016\/j.phymed.2023.155191_bib0002","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/s12929-019-0568-z","article-title":"Tumor-associated macrophages: an accomplice in solid tumor progression","volume":"26","author":"Chen","year":"2019","journal-title":"J. Biomed. Sci."},{"key":"10.1016\/j.phymed.2023.155191_bib0003","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/j.biopha.2016.07.054","article-title":"The effects of tanshinone IIA on hypoxia\/reoxygenation-induced myocardial microvascular endothelial cell apoptosis in rats via the JAK2\/STAT3 signaling pathway","volume":"83","author":"Cui","year":"2016","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.phymed.2023.155191_bib0004","doi-asserted-by":"crossref","first-page":"2492","DOI":"10.1016\/S0140-6736(17)31046-2","article-title":"Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1\/2 dose escalation and expansion trial","volume":"389","author":"El-Khoueiry","year":"2017","journal-title":"Lancet"},{"key":"10.1016\/j.phymed.2023.155191_bib0005","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1080\/14737140.2018.1535315","article-title":"Nivolumab for the treatment of hepatocellular carcinoma","volume":"18","author":"Finkelmeier","year":"2018","journal-title":"Expert Rev. Anticancer. Ther."},{"key":"10.1016\/j.phymed.2023.155191_bib0006","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1152\/physrev.00038.2010","article-title":"Normalization of the vasculature for treatment of cancer and other diseases","volume":"91","author":"Goel","year":"2011","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.phymed.2023.155191_bib0007","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1093\/neuonc\/noab181","article-title":"ELTD1 deletion reduces vascular abnormality and improves T-cell recruitment after PD-1 blockade in glioma","volume":"24","author":"Huang","year":"2022","journal-title":"Neuro Oncol."},{"key":"10.1016\/j.phymed.2023.155191_bib0008","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/nri.2017.145","article-title":"Improving immune-vascular crosstalk for cancer immunotherapy","volume":"18","author":"Huang","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.phymed.2023.155191_bib0009","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/j.it.2022.07.002","article-title":"High endothelial venules as potential gateways for therapeutics","volume":"43","author":"Hussain","year":"2022","journal-title":"Trends Immunol."},{"key":"10.1016\/j.phymed.2023.155191_bib0010","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1038\/nm0901-987","article-title":"Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy","volume":"7","author":"Jain","year":"2001","journal-title":"Nat. Med."},{"key":"10.1016\/j.phymed.2023.155191_bib0011","doi-asserted-by":"crossref","first-page":"6731","DOI":"10.1126\/scitranslmed.abb6731","article-title":"Dual role of endothelial Myct1 in tumor angiogenesis and tumor immunity","volume":"13","author":"Kabir","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.phymed.2023.155191_bib0012","doi-asserted-by":"crossref","first-page":"2415","DOI":"10.7150\/jca.24406","article-title":"ELTD1 function in hepatocellular carcinoma is carcinoma-associated fibroblast-dependent","volume":"9","author":"Kan","year":"2018","journal-title":"J. Cancer"},{"key":"10.1016\/j.phymed.2023.155191_bib0013","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/nrclinonc.2018.9","article-title":"Improving immunotherapy outcomes with anti-angiogenic treatments and vice versa","volume":"15","author":"Khan","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"10.1016\/j.phymed.2023.155191_bib0014","doi-asserted-by":"crossref","first-page":"109217","DOI":"10.18632\/oncotarget.22649","article-title":"Tanshinone IIA inhibits angiogenesis in human endothelial progenitor cells in vitro and in vivo","volume":"8","author":"Lee","year":"2017","journal-title":"Oncotarget"},{"key":"10.1016\/j.phymed.2023.155191_bib0015","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1186\/s12943-019-1047-6","article-title":"Current perspectives on the immunosuppressive tumor microenvironment in hepatocellular carcinoma: challenges and opportunities","volume":"18","author":"Lu","year":"2019","journal-title":"Mol. Cancer"},{"key":"10.1016\/j.phymed.2023.155191_bib0016","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.actbio.2022.10.032","article-title":"A theranostic metallodrug modulates immunovascular crosstalk to combat immunosuppressive liver cancer","volume":"154","author":"Luo","year":"2022","journal-title":"Acta Biomater."},{"key":"10.1016\/j.phymed.2023.155191_bib0017","first-page":"1337","article-title":"Research on the inhibiting effect of tanshinone IIA on colon cancer cell growth via COX-2-Wnt\/\u03b2-catenin signaling pathway","volume":"23","author":"Ma","year":"2018","journal-title":"J. BUON"},{"key":"10.1016\/j.phymed.2023.155191_bib0018","doi-asserted-by":"crossref","DOI":"10.1016\/j.smim.2021.101481","article-title":"The role of dendritic cells in cancer and anti-tumor immunity","volume":"52","author":"Marciscano","year":"2021","journal-title":"Semin. Immunol."},{"key":"10.1016\/j.phymed.2023.155191_bib0019","doi-asserted-by":"crossref","first-page":"4150","DOI":"10.1074\/jbc.M004814200","article-title":"ETL, a novel seven-transmembrane receptor that is developmentally regulated in the heart. ETL is a member of the secretin family and belongs to the epidermal growth factor-seven-transmembrane subfamily","volume":"276","author":"Nechiporuk","year":"2001","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.phymed.2023.155191_bib0020","doi-asserted-by":"crossref","first-page":"5207","DOI":"10.3390\/cancers13205207","article-title":"Improved immunotherapy efficacy by vascular modulation","volume":"13","author":"Newport","year":"2021","journal-title":"Cancers (Basel)"},{"key":"10.1016\/j.phymed.2023.155191_bib0021","article-title":"CU06-1004-induced vascular normalization improves immunotherapy by modulating tumor microenvironment via cytotoxic T cells","volume":"11","author":"Park","year":"2020","journal-title":"Front. Immunol."},{"key":"10.1016\/j.phymed.2023.155191_bib0022","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2022.106333","article-title":"Pharmacological manipulation of Ezh2 with salvianolic acid B results in tumor vascular normalization and synergizes with cisplatin and T cell-mediated immunotherapy","volume":"182","author":"Qian","year":"2022","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.phymed.2023.155191_bib0023","doi-asserted-by":"crossref","first-page":"637","DOI":"10.2217\/imt-2021-0026","article-title":"Atezolizumab in advanced hepatocellular carcinoma: good things come to those who wait","volume":"13","author":"Rizzo","year":"2021","journal-title":"Immunotherapy"},{"key":"10.1016\/j.phymed.2023.155191_bib0024","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.cell.2019.01.008","article-title":"A Paradigm Shift in Cancer Immunotherapy: from Enhancement to Normalization","volume":"176","author":"Sanmamed","year":"2019","journal-title":"Cell"},{"key":"10.1016\/j.phymed.2023.155191_bib0025","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1007\/s00262-022-03349-4","article-title":"Complete remissions following immunotherapy or immuno-oncology combinations in cancer patients: the MOUSEION-03 meta-analysis","volume":"72","author":"Santoni","year":"2023","journal-title":"Cancer Immunol. Immunother."},{"key":"10.1016\/j.phymed.2023.155191_bib0026","doi-asserted-by":"crossref","DOI":"10.1016\/j.critrevonc.2022.103596","article-title":"The impact of gender on The efficacy of immune checkpoint inhibitors in cancer patients: the MOUSEION-01 study","volume":"170","author":"Santoni","year":"2022","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"10.1016\/j.phymed.2023.155191_bib0027","doi-asserted-by":"crossref","first-page":"C1213","DOI":"10.1152\/ajpcell.00558.2003","article-title":"The tight junction: a multifunctional complex","volume":"286","author":"Schneeberger","year":"2004","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"10.1016\/j.phymed.2023.155191_bib0028","doi-asserted-by":"crossref","DOI":"10.3390\/ijms22105151","article-title":"ELTD1-an emerging silent actor in cancer drama play","volume":"22","author":"Sevastre","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.phymed.2023.155191_bib0029","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1002\/hep.30889","article-title":"Dual programmed death receptor-1 and vascular endothelial growth factor receptor-2 blockade promotes vascular normalization and enhances antitumor immune responses in hepatocellular carcinoma","volume":"71","author":"Shigeta","year":"2020","journal-title":"Hepatology"},{"key":"10.1016\/j.phymed.2023.155191_bib0030","doi-asserted-by":"crossref","first-page":"3048","DOI":"10.7150\/ijbs.62293","article-title":"ELTD1 promotes invasion and metastasis by activating MMP2 in colorectal cancer","volume":"17","author":"Sun","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"10.1016\/j.phymed.2023.155191_bib0031","first-page":"634","article-title":"[Tanshinone\u2161A attenuates carotid artery atherosclerosis by deactivating mast cells in adventitia]","volume":"47","author":"Sun","year":"2019","journal-title":"Zhonghua Xin Xue Guan Bing Za Zhi"},{"key":"10.1016\/j.phymed.2023.155191_bib0032","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1038\/nature21724","article-title":"Mutual regulation of tumour vessel normalization and immunostimulatory reprogramming","volume":"544","author":"Tian","year":"2017","journal-title":"Nature"},{"key":"10.1016\/j.phymed.2023.155191_bib0033","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s13045-022-01282-8","article-title":"Immunosuppressive cells in cancer: mechanisms and potential therapeutic targets","volume":"15","author":"Tie","year":"2022","journal-title":"J. Hematol. Oncol."},{"key":"10.1016\/j.phymed.2023.155191_bib0034","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.canlet.2011.06.031","article-title":"Anti-angiogenic effect of Tanshinone IIA involves inhibition of matrix invasion and modification of MMP-2\/TIMP-2 secretion in vascular endothelial cells","volume":"310","author":"Tsai","year":"2011","journal-title":"Cancer Lett."},{"key":"10.1016\/j.phymed.2023.155191_bib0035","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/s10456-017-9562-9","article-title":"Tumor angiogenesis and vascular normalization: alternative therapeutic targets","volume":"20","author":"Viallard","year":"2017","journal-title":"Angiogenesis"},{"key":"10.1016\/j.phymed.2023.155191_bib0036","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/1756-8722-5-69","article-title":"Tanshinone IIA inhibits metastasis after palliative resection of hepatocellular carcinoma and prolongs survival in part via vascular normalization","volume":"5","author":"Wang","year":"2012","journal-title":"J. Hematol. Oncol."},{"key":"10.1016\/j.phymed.2023.155191_bib0037","doi-asserted-by":"crossref","first-page":"3244","DOI":"10.1166\/jbn.2014.1982","article-title":"Targeted delivery of tanshinone IIA-conjugated mPEG-PLGA-PLL-cRGD nanoparticles to hepatocellular carcinoma","volume":"10","author":"Wang","year":"2014","journal-title":"J. Biomed. Nanotechnol."},{"key":"10.1016\/j.phymed.2023.155191_bib0038","doi-asserted-by":"crossref","first-page":"163","DOI":"10.3892\/or.2014.3592","article-title":"Anti-angiogenic effect of tanshinone IIA involves inhibition of the VEGF\/VEGFR2 pathway in vascular endothelial cells","volume":"33","author":"Xing","year":"2015","journal-title":"Oncol. Rep."},{"key":"10.1016\/j.phymed.2023.155191_bib0039","doi-asserted-by":"crossref","DOI":"10.3390\/ijms22010241","article-title":"ABL001, a bispecific antibody targeting VEGF and DLL4, with chemotherapy, synergistically inhibits tumor progression in xenograft models","volume":"22","author":"Yeom","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.phymed.2023.155191_bib0040","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1177\/030089160909500623","article-title":"Tanshinone II-A inhibits invasion and metastasis of human hepatocellular carcinoma cells in vitro and in vivo","volume":"95","author":"Yuxian","year":"2009","journal-title":"Tumori"},{"key":"10.1016\/j.phymed.2023.155191_bib0041","doi-asserted-by":"crossref","first-page":"751","DOI":"10.2174\/1381612828666211224152440","article-title":"Sodium tanshinone IIA sulfonate improves adverse ventricular remodeling post MI by reducing myocardial necrosis, modulating inflammation and promoting angiogenesis","volume":"28","author":"Zhang","year":"2021","journal-title":"Curr. Pharm. Des."},{"key":"10.1016\/j.phymed.2023.155191_bib0042","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/S0254-6272(18)30980-4","article-title":"Tanshinone II improves distribution and anti-tumor efficacy of pegylated liposomal doxorubicin via normalizing the structure and function of tumor vasculature in hepa1-6 hepatoma mice model","volume":"38","author":"Zhang","year":"2018","journal-title":"J. Tradit. Chin. Med."},{"key":"10.1016\/j.phymed.2023.155191_bib0043","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1007\/s00432-021-03633-3","article-title":"Apatinib combined with PD-L1 blockade synergistically enhances antitumor immune responses and promotes HEV formation in gastric cancer","volume":"147","author":"Zhang","year":"2021","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"10.1016\/j.phymed.2023.155191_bib0044","doi-asserted-by":"crossref","DOI":"10.1002\/jbt.21903","article-title":"Sodium tanshinone IIA sulfonate prevents hypoxic trophoblast-induced endothelial cell dysfunction via targeting HMGB1 release","volume":"31","author":"Zhao","year":"2017","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"10.1016\/j.phymed.2023.155191_bib0045","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.21037\/atm-20-5741","article-title":"Tanshinone IIA suppresses ovarian cancer growth through inhibiting malignant properties and angiogenesis","volume":"8","author":"Zhou","year":"2020","journal-title":"Ann. Transl. Med."},{"key":"10.1016\/j.phymed.2023.155191_bib0046","first-page":"1159","article-title":"Tanshinone IIA reduces secretion of pro\u2011angiogenic factors and inhibits angiogenesis in human colorectal cancer","volume":"43","author":"Zhou","year":"2020","journal-title":"Oncol. Rep."},{"key":"10.1016\/j.phymed.2023.155191_bib0047","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.ejphar.2012.09.051","article-title":"Mechanism of reversal of high glucose-induced endothelial nitric oxide synthase uncoupling by tanshinone IIA in human endothelial cell line EA.hy926","volume":"697","author":"Zhou","year":"2012","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.phymed.2023.155191_bib0048","first-page":"175","article-title":"ELTD1, an effective anti-angiogenic target for gliomas: preclinical assessment in mouse GL261 and human G55 xenograft glioma models","volume":"19","author":"Ziegler","year":"2017","journal-title":"Neuro Oncol."}],"container-title":["Phytomedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711323005500?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711323005500?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T18:51:45Z","timestamp":1760554305000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0944711323005500"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1]]},"references-count":48,"alternative-id":["S0944711323005500"],"URL":"https:\/\/doi.org\/10.1016\/j.phymed.2023.155191","relation":{},"ISSN":["0944-7113"],"issn-type":[{"value":"0944-7113","type":"print"}],"subject":[],"published":{"date-parts":[[2024,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Tanshinone IIA normalized hepatocellular carcinoma vessels and enhanced PD-1 inhibitor efficacy by inhibiting ELTD1","name":"articletitle","label":"Article Title"},{"value":"Phytomedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phymed.2023.155191","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 Elsevier GmbH. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"155191"}}