{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:31:06Z","timestamp":1790857866347,"version":"4.1.0"},"reference-count":57,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,12,28]],"date-time":"2024-12-28T00:00:00Z","timestamp":1735344000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Advanced Research"],"published-print":{"date-parts":[[2025,10]]},"DOI":"10.1016\/j.jare.2024.12.045","type":"journal-article","created":{"date-parts":[[2025,1,5]],"date-time":"2025-01-05T01:33:14Z","timestamp":1736040794000},"page":"731-744","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":17,"special_numbering":"C","title":["Parkin modulates the hepatocellular carcinoma microenvironment by regulating PD-1\/PD-L1 signalling"],"prefix":"10.1016","volume":"76","author":[{"given":"Guiqin","family":"Ye","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiuzhou","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maomao","family":"Pu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianbin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jare.2024.12.045_b0005","first-page":"7","article-title":"Cancer statistics, 2022","volume":"72","author":"Siegel","year":"2022","journal-title":"CA Cancer J Clin"},{"key":"10.1016\/j.jare.2024.12.045_b0010","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.pharmthera.2017.02.010","article-title":"Recent advances in hepatocellular carcinoma therapy","volume":"173","author":"Dutta","year":"2017","journal-title":"Pharmacol Ther"},{"key":"10.1016\/j.jare.2024.12.045_b0015","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.jare.2024.12.045_b0020","doi-asserted-by":"crossref","DOI":"10.3390\/cancers12030738","article-title":"Review of Indications of FDA-Approved Immune Checkpoint Inhibitors per NCCN Guidelines with the Level of Evidence","volume":"12","author":"Vaddepally","year":"2020","journal-title":"Cancers (Basel)"},{"key":"10.1016\/j.jare.2024.12.045_b0025","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1158\/2159-8290.CD-18-0367","article-title":"Fundamental Mechanisms of Immune Checkpoint Blockade Therapy","volume":"8","author":"Wei","year":"2018","journal-title":"Cancer Discov"},{"key":"10.1016\/j.jare.2024.12.045_b0030","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1038\/70932","article-title":"B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion","volume":"5","author":"Dong","year":"1999","journal-title":"Nat Med"},{"key":"10.1016\/j.jare.2024.12.045_b0035","doi-asserted-by":"crossref","unstructured":"Xin Yu, J., J. P. Hodge, C. Oliva, et al., Trends in clinical development for PD-1\/PD-L1 inhibitors, Nat Rev Drug Discov. 19 (2020) 163-164.","DOI":"10.1038\/d41573-019-00182-w"},{"key":"10.1016\/j.jare.2024.12.045_b0040","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/s41571-019-0203-7","article-title":"Navigating metabolic pathways to enhance antitumour immunity and immunotherapy","volume":"16","author":"Li","year":"2019","journal-title":"Nat Rev Clin Oncol"},{"key":"10.1016\/j.jare.2024.12.045_b0045","doi-asserted-by":"crossref","DOI":"10.1016\/j.canlet.2022.216038","article-title":"Immune checkpoint inhibitor resistance in hepatocellular carcinoma","volume":"555","author":"Wang","year":"2023","journal-title":"Cancer Lett"},{"key":"10.1016\/j.jare.2024.12.045_b0050","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.ccell.2021.12.009","article-title":"MEK inhibition overcomes chemoimmunotherapy resistance by inducing CXCL10 in cancer cells","volume":"40","author":"Limagne","year":"2022","journal-title":"Cancer Cell"},{"key":"10.1016\/j.jare.2024.12.045_b0055","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/s41422-022-00766-z","article-title":"Targeting ATAD3A-PINK1-mitophagy axis overcomes chemoimmunotherapy resistance by redirecting PD-L1 to mitochondria","volume":"33","author":"Xie","year":"2023","journal-title":"Cell Res"},{"key":"10.1016\/j.jare.2024.12.045_b0060","first-page":"1143","article-title":"Ethanol-induced mitophagy in liver is associated with activation of the PINK1-Parkin pathway triggered by oxidative DNA damage","volume":"31","author":"Eid","year":"2016","journal-title":"Histol Histopathol"},{"key":"10.1016\/j.jare.2024.12.045_b0065","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/cdd.2012.81","article-title":"The pathways of mitophagy for quality control and clearance of mitochondria","volume":"20","author":"Ashrafi","year":"2013","journal-title":"Cell Death Differ"},{"key":"10.1016\/j.jare.2024.12.045_b0070","doi-asserted-by":"crossref","DOI":"10.3390\/cells9040837","article-title":"Role and Mechanisms of Mitophagy in Liver Diseases","volume":"9","author":"Ma","year":"2020","journal-title":"Cells"},{"key":"10.1016\/j.jare.2024.12.045_b0075","doi-asserted-by":"crossref","first-page":"5035","DOI":"10.3892\/mmr.2015.4029","article-title":"Promotion of mitochondrial energy metabolism during hepatocyte apoptosis in a rat model of acute liver failure","volume":"12","author":"Chen","year":"2015","journal-title":"Mol Med Rep"},{"key":"10.1016\/j.jare.2024.12.045_b0080","doi-asserted-by":"crossref","first-page":"5274","DOI":"10.1038\/onc.2017.136","article-title":"Thyroid hormone protects hepatocytes from HBx-induced carcinogenesis by enhancing mitochondrial turnover","volume":"36","author":"Chi","year":"2017","journal-title":"Oncogene"},{"key":"10.1016\/j.jare.2024.12.045_b0085","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.cell.2018.05.028","article-title":"Mitophagy in Intestinal Epithelial Cells Triggers Adaptive Immunity during Tumorigenesis","volume":"174","author":"Ziegler","year":"2018","journal-title":"Cell"},{"key":"10.1016\/j.jare.2024.12.045_b0090","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1038\/onc.2016.302","article-title":"Parkin and mitophagy in cancer","volume":"36","author":"Bernardini","year":"2017","journal-title":"Oncogene"},{"key":"10.1016\/j.jare.2024.12.045_b0095","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.devcel.2018.07.012","article-title":"PINK1 and PARK2 Suppress Pancreatic Tumorigenesis through Control of Mitochondrial Iron-Mediated Immunometabolism","volume":"46","author":"Li","year":"2018","journal-title":"Dev Cell"},{"key":"10.1016\/j.jare.2024.12.045_b0100","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.cell.2016.05.039","article-title":"Parkinson's Disease-Related Proteins PINK1 and Parkin Repress Mitochondrial Antigen Presentation","volume":"166","author":"Matheoud","year":"2016","journal-title":"Cell"},{"key":"10.1016\/j.jare.2024.12.045_b0105","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1038\/s41590-020-0793-3","article-title":"Disturbed mitochondrial dynamics in CD8(+) TILs reinforce T cell exhaustion","volume":"21","author":"Yu","year":"2020","journal-title":"Nat Immunol"},{"key":"10.1016\/j.jare.2024.12.045_b0110","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1002\/hep.30191","article-title":"FUN14 Domain-Containing 1-Mediated Mitophagy Suppresses Hepatocarcinogenesis by Inhibition of Inflammasome Activation in Mice","volume":"69","author":"Li","year":"2019","journal-title":"Hepatology"},{"key":"10.1016\/j.jare.2024.12.045_b0115","doi-asserted-by":"crossref","first-page":"5007","DOI":"10.1038\/s41388-019-0772-z","article-title":"Mitochondrial fission-induced mtDNA stress promotes tumor-associated macrophage infiltration and HCC progression","volume":"38","author":"Bao","year":"2019","journal-title":"Oncogene"},{"key":"10.1016\/j.jare.2024.12.045_b0120","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.cell.2020.11.041","article-title":"Single-cell landscape of the ecosystem in early-relapse hepatocellular carcinoma","volume":"184","author":"Sun","year":"2021","journal-title":"Cell"},{"key":"10.1016\/j.jare.2024.12.045_b0125","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1093\/clinchem\/hvab116","article-title":"Single Cell and Plasma RNA Sequencing for RNA Liquid Biopsy for Hepatocellular Carcinoma","volume":"67","author":"Vong","year":"2021","journal-title":"Clin Chem"},{"key":"10.1016\/j.jare.2024.12.045_b0130","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/s13046-021-01874-1","article-title":"Single-cell RNA sequencing in cancer research","volume":"40","author":"Zhang","year":"2021","journal-title":"J Exp Clin Cancer Res"},{"key":"10.1016\/j.jare.2024.12.045_b0135","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1016\/j.cell.2017.05.035","article-title":"Landscape of Infiltrating T Cells in Liver Cancer Revealed by Single-Cell Sequencing","volume":"169","author":"Zheng","year":"2017","journal-title":"Cell"},{"key":"10.1016\/j.jare.2024.12.045_b0140","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/j.cell.2019.10.003","article-title":"Landscape and Dynamics of Single Immune Cells in Hepatocellular Carcinoma","volume":"179","author":"Zhang","year":"2019","journal-title":"Cell"},{"key":"10.1016\/j.jare.2024.12.045_b0145","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/978-981-15-4494-1_2","article-title":"Methods for Single-Cell Isolation and Preparation","volume":"1255","author":"Pensold","year":"2020","journal-title":"Advances in Experimental Medicine and Biology"},{"key":"10.1016\/j.jare.2024.12.045_b0150","doi-asserted-by":"crossref","DOI":"10.1111\/cpr.13327","article-title":"Mitophagy: A novel perspective for insighting into cancer and cancer treatment","volume":"55","author":"Song","year":"2022","journal-title":"Cell Prolif"},{"key":"10.1016\/j.jare.2024.12.045_b0155","doi-asserted-by":"crossref","first-page":"43628","DOI":"10.1074\/jbc.M308947200","article-title":"Parkin-deficient mice exhibit nigrostriatal deficits but not loss of dopaminergic neurons","volume":"278","author":"Goldberg","year":"2003","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jare.2024.12.045_b0160","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1136\/gutjnl-2019-319227","article-title":"TREM-2 defends the liver against hepatocellular carcinoma through multifactorial protective mechanisms","volume":"70","author":"Esparza-Baquer","year":"2021","journal-title":"Gut"},{"key":"10.1016\/j.jare.2024.12.045_b0165","first-page":"2223","article-title":"Special considerations in interpreting liver function tests","volume":"59","author":"Johnston","year":"1999","journal-title":"Am Fam Physician"},{"key":"10.1016\/j.jare.2024.12.045_b0170","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1515\/hsz-2012-0119","article-title":"Mitophagy: mechanisms, pathophysiological roles, and analysis","volume":"393","author":"Ding","year":"2012","journal-title":"Biol Chem"},{"key":"10.1016\/j.jare.2024.12.045_b0175","doi-asserted-by":"crossref","first-page":"4182","DOI":"10.1080\/15548627.2021.1907167","article-title":"The role of mitophagy in the regulation of mitochondrial energetic status in neurons","volume":"17","author":"Han","year":"2021","journal-title":"Autophagy"},{"key":"10.1016\/j.jare.2024.12.045_b0180","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbcan.2022.188720","article-title":"Understanding initiation and progression of hepatocellular carcinoma through single cell sequencing","volume":"1877","author":"Li","year":"2022","journal-title":"Biochim Biophys Acta Rev Cancer"},{"key":"10.1016\/j.jare.2024.12.045_b0185","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1038\/s41596-020-0292-x","article-title":"CellPhoneDB: inferring cell-cell communication from combined expression of multi-subunit ligand-receptor complexes","volume":"15","author":"Efremova","year":"2020","journal-title":"Nat Protoc"},{"key":"10.1016\/j.jare.2024.12.045_b0190","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/j.cell.2020.07.013","article-title":"TREM2 Modulation Remodels the Tumor Myeloid Landscape Enhancing Anti-PD-1 Immunotherapy","volume":"182","author":"Molgora","year":"2020","journal-title":"Cell"},{"key":"10.1016\/j.jare.2024.12.045_b0195","doi-asserted-by":"crossref","first-page":"6662","DOI":"10.1073\/pnas.1121623109","article-title":"The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors","volume":"109","author":"Willingham","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.jare.2024.12.045_b0200","doi-asserted-by":"crossref","first-page":"6246","DOI":"10.1038\/onc.2016.160","article-title":"MIF-CD74 signaling impedes microglial M1 polarization and facilitates brain tumorigenesis","volume":"35","author":"Ghoochani","year":"2016","journal-title":"Oncogene"},{"key":"10.1016\/j.jare.2024.12.045_b0205","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1110\/ps.03479604","article-title":"Predicting subcellular localization of proteins for Gram-negative bacteria by support vector machines based on n-peptide compositions","volume":"13","author":"Yu","year":"2004","journal-title":"Protein Sci"},{"key":"10.1016\/j.jare.2024.12.045_b0210","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1038\/s41392-023-01503-7","article-title":"The mitophagy pathway and its implications in human diseases","volume":"8","author":"Wang","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"10.1016\/j.jare.2024.12.045_b0215","doi-asserted-by":"crossref","first-page":"4816","DOI":"10.1021\/acsnano.0c00708","article-title":"Icaritin Exacerbates Mitophagy and Synergizes with Doxorubicin to Induce Immunogenic Cell Death in Hepatocellular Carcinoma","volume":"14","author":"Yu","year":"2020","journal-title":"ACS Nano"},{"key":"10.1016\/j.jare.2024.12.045_b0220","doi-asserted-by":"crossref","first-page":"29231","DOI":"10.1074\/jbc.M110.108241","article-title":"Parkin enhances the expression of cyclin-dependent kinase 6 and negatively regulates the proliferation of breast cancer cells","volume":"285","author":"Tay","year":"2010","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jare.2024.12.045_b0225","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.4161\/cc.24215","article-title":"Parkin deficiency contributes to pancreatic tumorigenesis by inducing spindle multipolarity and misorientation","volume":"12","author":"Sun","year":"2013","journal-title":"Cell Cycle"},{"key":"10.1016\/j.jare.2024.12.045_b0230","doi-asserted-by":"crossref","first-page":"5956","DOI":"10.1073\/pnas.0931262100","article-title":"Parkin, a gene implicated in autosomal recessive juvenile parkinsonism, is a candidate tumor suppressor gene on chromosome 6q25-q27","volume":"100","author":"Cesari","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.jare.2024.12.045_b0235","doi-asserted-by":"crossref","first-page":"8370","DOI":"10.1038\/sj.onc.1207072","article-title":"Alterations in the common fragile site gene Parkin in ovarian and other cancers","volume":"22","author":"Denison","year":"2003","journal-title":"Oncogene"},{"key":"10.1016\/j.jare.2024.12.045_b0240","doi-asserted-by":"crossref","first-page":"2720","DOI":"10.1158\/1078-0432.CCR-03-0086","article-title":"Alterations of the tumor suppressor gene Parkin in non-small cell lung cancer","volume":"10","author":"Picchio","year":"2004","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.jare.2024.12.045_b0245","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1038\/s41419-019-1881-x","article-title":"Parkin facilitates proteasome inhibitor-induced apoptosis via suppression of NF-\u03baB activity in hepatocellular carcinoma","volume":"10","author":"Zhang","year":"2019","journal-title":"Cell Death Dis"},{"key":"10.1016\/j.jare.2024.12.045_b0250","doi-asserted-by":"crossref","first-page":"6002","DOI":"10.1038\/onc.2008.199","article-title":"Parkin as a tumor suppressor gene for hepatocellular carcinoma","volume":"27","author":"Fujiwara","year":"2008","journal-title":"Oncogene"},{"key":"10.1016\/j.jare.2024.12.045_b0255","doi-asserted-by":"crossref","DOI":"10.1172\/JCI180983","article-title":"Parkin activates innate immunity and promotes antitumor immune responses","volume":"134","author":"Perego","year":"2024","journal-title":"J Clin Invest"},{"key":"10.1016\/j.jare.2024.12.045_b0260","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.immuni.2018.12.021","article-title":"Intratumoral Tcf1(+)PD-1(+)CD8(+) T Cells with Stem-like Properties Promote Tumor Control in Response to Vaccination and Checkpoint Blockade Immunotherapy","volume":"50","author":"Siddiqui","year":"2019","journal-title":"Immunity"},{"key":"10.1016\/j.jare.2024.12.045_b0265","doi-asserted-by":"crossref","DOI":"10.1016\/j.redox.2022.102342","article-title":"Metformin modulates mitochondrial function and mitophagy in peripheral blood mononuclear cells from type 2 diabetic patients","volume":"53","author":"de Mara\u00f1\u00f3n","year":"2022","journal-title":"Redox Biol"},{"key":"10.1016\/j.jare.2024.12.045_b0270","doi-asserted-by":"crossref","DOI":"10.1155\/2021\/5529913","article-title":"Quercetin Improves Cardiomyocyte Vulnerability to Hypoxia by Regulating SIRT1\/TMBIM6-Related Mitophagy and Endoplasmic Reticulum Stress","volume":"2021","author":"Chang","year":"2021","journal-title":"Oxid Med Cell Longev"},{"key":"10.1016\/j.jare.2024.12.045_b0275","doi-asserted-by":"crossref","first-page":"2936","DOI":"10.1182\/blood-2009-05-220111","article-title":"Monocytes promote tumor cell survival in T-cell lymphoproliferative disorders and are impaired in their ability to differentiate into mature dendritic cells","volume":"114","author":"Wilcox","year":"2009","journal-title":"Blood"},{"key":"10.1016\/j.jare.2024.12.045_b0280","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1158\/2159-8290.CD-19-0958","article-title":"Regulatory T-cell Depletion Alters the Tumor Microenvironment and Accelerates Pancreatic Carcinogenesis","volume":"10","author":"Zhang","year":"2020","journal-title":"Cancer Discov"},{"key":"10.1016\/j.jare.2024.12.045_b0285","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.semcancer.2021.04.002","article-title":"Post-translational regulations of PD-L1 and PD-1: Mechanisms and opportunities for combined immunotherapy","volume":"85","author":"Dai","year":"2022","journal-title":"Semin Cancer Biol"}],"container-title":["Journal of Advanced Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2090123224006234?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2090123224006234?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T21:04:43Z","timestamp":1759784683000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2090123224006234"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":57,"alternative-id":["S2090123224006234"],"URL":"https:\/\/doi.org\/10.1016\/j.jare.2024.12.045","relation":{},"ISSN":["2090-1232"],"issn-type":[{"value":"2090-1232","type":"print"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Parkin modulates the hepatocellular carcinoma microenvironment by regulating PD-1\/PD-L1 signalling","name":"articletitle","label":"Article Title"},{"value":"Journal of Advanced Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jare.2024.12.045","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 Published by Elsevier B.V. on behalf of Cairo University.","name":"copyright","label":"Copyright"}]}}