{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T05:48:07Z","timestamp":1782712087277,"version":"3.54.5"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U2004119, 82572338"],"award-info":[{"award-number":["U2004119, 82572338"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We hypothesized that preoperative administration of liposome arsenic trioxide (LATO) would downregulate hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) in residual tumors following incomplete radiofrequency ablation (iRFA), thereby modulating the tumor microenvironment, suppressing residual tumor proliferation and angiogenesis, and consequently enhancing the antitumor efficacy of programmed death-ligand 1 (PD-L1) blockade.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using a murine Hepa1\u20136 hepatocellular carcinoma model subjected to incomplete radiofrequency iRFA, cohorts were stratified based on preoperative LATO administration and postoperative anti-PD-L1 antibody combination therapy, and the indexes such as proliferation and immune infiltration of residual tumor were tested respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      After iRFA, residual tumors exhibited significant up-regulation of PCNA, CD31, and HIF-1\u03b1 compared with the control group (all\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.0001). Intravenous infusion of LATO before RFA could significantly decrease the expression of PCNA, CD31 and HIF-1\u03b1 in the residual tumor, promote the infiltration of immune cells (CD4\n                      <jats:sup>+<\/jats:sup>\n                      , CD8\n                      <jats:sup>+<\/jats:sup>\n                      ) and prolong the survival time of mice. After RFA, combined use of anti-PD-L1 antibody can further reduce the expression of cell proliferation and tumor proliferation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Pre-treatment with LATO prior to RFA appears to modulate the tumor microenvironment, which may contribute to improved ablation efficacy and help restrain the progression of residual tumors. Furthermore, it could potentially enhance the antitumor effect of combining RFA with anti-PD-L1 antibody therapy by sensitizing the tumor immune response.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1776060","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T05:40:51Z","timestamp":1782711651000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanism of liposome arsenic trioxide regulating tumor microenvironment and sensitizing tumor immune response after radiofrequency ablation"],"prefix":"10.3389","volume":"17","author":[{"given":"Chao","family":"Liang","sequence":"first","affiliation":[{"name":"Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuguang","family":"Ju","sequence":"additional","affiliation":[{"name":"Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daqian","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiacheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyang","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianzhuang","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinwei","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuhua","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3109\/02656736.2013.821528","article-title":"Radiofrequency ablation for hepatocellular carcinoma","volume":"29","author":"Nishikawa","year":"2013","journal-title":"Int J Hyperthermia"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/s1055-3207(23)00082-0","article-title":"Outcomes of radiofrequency ablation as first-line therapy for hepatocellular carcinoma less than 3 cm in potentially transplantable patients","volume":"70","author":"Doyle","year":"2019","journal-title":"J Hepatol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2018172028","article-title":"Medium or large hepatocellular carcinoma: Sorafenib combined with transarterial chemoembolization and radiofrequency ablation","volume":"288","author":"Zhu","year":"2018","journal-title":"Radiology"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.01.014","article-title":"No-touch multibipolar radiofrequency ablation vs. surgical resection for solitary hepatocellular carcinoma ranging from 2 to 5 cm","volume":"68","author":"Mohkam","year":"2018","journal-title":"J Hepatol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0037266","article-title":"Insufficient radiofrequency ablation promotes angiogenesis of residual hepatocellular carcinoma via HIF-1\u03b1\/VEGFA","volume":"7","author":"Kong","year":"2012","journal-title":"PloS One"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1080\/02656736.2022.2093995","article-title":"Arsenic trioxide inhibits angiogenesis of hepatocellular carcinoma after insufficient radiofrequency ablation via blocking paracrine angiopoietin-1 and angiopoietin-2","volume":"39","author":"Dong","year":"2022","journal-title":"Int J Hyperthermia"},{"key":"B8","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.lfs.2018.05.006","article-title":"Arsenic trioxide induces apoptosis and inhibits the growth of human liver cancer cells","volume":"205","author":"Sadaf","year":"2018","journal-title":"Life Sci"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20131916","article-title":"PD-L1 is a novel direct target of HIF-1\u03b1, and its blockade under hypoxia enhanced MDSC-mediated T cell activation","volume":"211","author":"Noman","year":"2014","journal-title":"J Exp Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/s00330-019-06189-6","article-title":"Radiofrequency ablation of liver metastasis: potential impact on immune checkpoint inhibitor therapy","volume":"29","author":"Minami","year":"2019","journal-title":"Eur Radiol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(20)30011-5","article-title":"Camrelizumab in patients with previously treated advanced hepatocellular carcinoma: a multicentre, open-label, parallel-group, randomised, phase 2 trial","volume":"21","author":"Qin","year":"2020","journal-title":"Lancet Oncol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/5773802","article-title":"Exploring the mechanisms of arsenic trioxide (Pishuang) in hepatocellular carcinoma based on network pharmacology","volume":"2021","author":"Wang","year":"2021","journal-title":"Evid Based Complement Alternat Med"},{"key":"B13","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.canlet.2010.10.022","article-title":"Genistein potentiates the effect of arsenic trioxide against human hepatocellular carcinoma: role of Akt and nuclear factor-\u03baB","volume":"301","author":"Ma","year":"2011","journal-title":"Cancer Lett"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphotobiol.2015.03.001","article-title":"Arsenic trioxide binding to serum proteins","volume":"148","author":"Shooshtary","year":"2015","journal-title":"J\u00a0Photochem Photobiol B"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.229583","article-title":"Oral arsenic trioxide ORH-2014 pharmacokinetic and safety profile in patients with advanced hematologic disorders","volume":"105","author":"Ravandi","year":"2020","journal-title":"Haematologica"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s12012-018-09504-7","article-title":"An overview on arsenic trioxide-induced cardiotoxicity","volume":"19","author":"Vineetha","year":"2019","journal-title":"Cardiovasc Toxicol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2018.11.008","article-title":"In vitro stability of arsenic trioxide-liposome encapsulates for acute promyelocytic leukemia treatment","volume":"76","author":"da Rosa","year":"2019","journal-title":"Leuk Res"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.2147\/cmar.s199188","article-title":"Hepatic arterial chemoembolization with arsenic trioxide eluting CalliSpheres microspheres versus lipiodol emulsion: pharmacokinetics and intratumoral concentration in a rabbit liver tumor model","volume":"11","author":"Duan","year":"2019","journal-title":"Cancer Manag Res"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.112585","article-title":"Blocking TGF\u03b2R synergistically enhances anti-tumor effects of anti-PD-1 antibody in a mouse model of incomplete thermal ablation","volume":"138","author":"Ju","year":"2024","journal-title":"Int Immunopharmacol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1580","DOI":"10.1016\/j.cmet.2023.07.001","article-title":"Tumor aerobic glycolysis confers immune evasion through modulating sensitivity to T cell-mediated bystander killing via TNF-\u03b1","volume":"35","author":"Wu","year":"2023","journal-title":"Cell Metab"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00566-3","article-title":"Interferon-\u03b3: teammate or opponent in the tumour microenvironment","volume":"22","author":"Gocher","year":"2022","journal-title":"Nat Rev Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.214.3.r00mr02761","article-title":"Hepatocellular carcinoma: radio-frequency ablation of medium and large lesions","volume":"214","author":"Livraghi","year":"2000","journal-title":"Radiology"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1080\/02656736.2022.2059581","article-title":"Radiofrequency ablation in the treatment of hepatocellular carcinoma","volume":"39","author":"Deng","year":"2022","journal-title":"Int J Hyperthermia"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1097\/sla.0b013e3181a38ef5","article-title":"Accelerated perinecrotic outgrowth of colorectal liver metastases following radiofrequency ablation is a hypoxia-driven phenomenon","volume":"249","author":"Nijkamp","year":"2009","journal-title":"Ann Surg"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.04.040","article-title":"CD95 is a key mediator of invasion and accelerated outgrowth of mouse colorectal liver metastases following radiofrequency ablation","volume":"53","author":"Nijkamp","year":"2010","journal-title":"J Hepatol"},{"key":"B26","article-title":"Arsenic trioxide causes selective necrosis in solid murine tumors by vascular shutdown","volume":"59","author":"Lew","year":"1999","journal-title":"Cancer Res"},{"key":"B27","doi-asserted-by":"publisher","first-page":"12677","DOI":"10.1038\/s41598-017-13010-1","article-title":"The influence of liposomal quercetin on liver damage induced by microwave ablation","volume":"7","author":"Duan","year":"2017","journal-title":"Sci Rep"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.1c00936","article-title":"Enhanced therapeutic effect of liposomal doxorubicin via bio-orthogonal chemical reactions in tumors","volume":"19","author":"Kannaka","year":"2022","journal-title":"Mol Pharm"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1002\/wnan.1846","article-title":"Pharmacokinetic behaviors of soft nanoparticulate formulations of chemotherapeutics","volume":"15","author":"Sarkar","year":"2023","journal-title":"Wiley Interdiscip Rev Nanomed Nanobiotechnol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2025.113642","article-title":"Quercetin liposomes conjugated with hyaluronidase: An efficient drug delivery system to block pancreatic cancer","volume":"382","author":"Sun","year":"2025","journal-title":"J Control Release"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.5582\/bst.2022.01373","article-title":"A well-matched marriage of immunotherapy and radiofrequency ablation to reduce the relapse and progression of hepatocellular carcinoma","volume":"16","author":"Liao","year":"2022","journal-title":"Biosci Trends"},{"key":"B32","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1038\/s41575-020-00395-0","article-title":"Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma","volume":"18","author":"Llovet","year":"2021","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-15-1352","article-title":"PD-1 blockade boosts radiofrequency ablation-elicited adaptive immune responses against tumor","volume":"22","author":"Shi","year":"2016","journal-title":"Clin Cancer Res"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1922","DOI":"10.3390\/cancers13081922","article-title":"Anti-PD-1\/PD-L1 based combination immunotherapy to boost antigen-specific CD8(+) T cell response in hepatocellular carcinoma","volume":"13","author":"Pe\u00f1a-Asensio","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.can-14-2598","article-title":"Mechanisms of hypoxia-mediated immune escape in cancer","volume":"74","author":"Barsoum","year":"2014","journal-title":"Cancer Res"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2018.02.014","article-title":"Association of PD-L1 and HIF-1\u03b1 coexpression with poor prognosis in hepatocellular carcinoma","volume":"11","author":"Dai","year":"2018","journal-title":"Transl Oncol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.580241","article-title":"Ablation reboots the response in advanced hepatocellular carcinoma with stable or atypical response during PD-1 therapy: a proof-of-concept study","volume":"10","author":"Lyu","year":"2020","journal-title":"Front Oncol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.792781","article-title":"Combination of ablation and immunotherapy for hepatocellular carcinoma: where we are and where to go","volume":"12","author":"Wang","year":"2021","journal-title":"Front Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1776060\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T05:40:52Z","timestamp":1782711652000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1776060\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,29]]},"references-count":38,"alternative-id":["10.3389\/fimmu.2026.1776060"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1776060","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,29]]},"article-number":"1776060"}}