{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T07:05:51Z","timestamp":1793689551293,"version":"4.5.1"},"reference-count":48,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"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"}]},{"DOI":"10.13039\/501100003395","name":"Shanghai Municipal Education Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003395","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007219","name":"Shanghai Municipal Natural Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cancer Letters"],"published-print":{"date-parts":[[2026,5]]},"DOI":"10.1016\/j.canlet.2026.218395","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T17:47:02Z","timestamp":1772473622000},"page":"218395","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"special_numbering":"C","title":["DysUFMylation reprograms immunosuppressive neutrophils to potentiate anti-PD-1 therapy in hepatocellular carcinoma"],"prefix":"10.1016","volume":"645","author":[{"given":"Xukang","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7268-7384","authenticated-orcid":false,"given":"Zeping","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiu","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yipeng","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqiang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4555-3947","authenticated-orcid":false,"given":"Song","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangjian","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mien-Chie","family":"Hung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenhao","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"3","key":"10.1016\/j.canlet.2026.218395_bib1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"issue":"20","key":"10.1016\/j.canlet.2026.218395_bib2","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.1056\/NEJMoa1915745","article-title":"Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma","volume":"382","author":"Finn","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.canlet.2026.218395_bib3","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.canlet.2019.12.002","article-title":"Immunotherapy for hepatocellular carcinoma","volume":"470","author":"Zongyi","year":"2020","journal-title":"Cancer Lett."},{"issue":"5","key":"10.1016\/j.canlet.2026.218395_bib4","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/s41591-018-0014-x","article-title":"Understanding the tumor immune microenvironment (TIME) for effective therapy","volume":"24","author":"Binnewies","year":"2018","journal-title":"Nat Med"},{"issue":"1","key":"10.1016\/j.canlet.2026.218395_bib5","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/cac2.12613","article-title":"Effect of neutrophils on tumor immunity and immunotherapy resistance with underlying mechanisms","volume":"45","author":"Yao","year":"2025","journal-title":"Cancer Commun."},{"key":"10.1016\/j.canlet.2026.218395_bib6","article-title":"Neutrophils in cancer drug resistance: roles and therapeutic opportunities","volume":"611","author":"Liu","year":"2024","journal-title":"Cancer Lett."},{"issue":"1","key":"10.1016\/j.canlet.2026.218395_bib7","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/s41392-025-02242-7","article-title":"Therapeutic potential of tumor-associated neutrophils: dual role and phenotypic plasticity","volume":"10","author":"Zhou","year":"2025","journal-title":"Signal Transduct. Targeted Ther."},{"key":"10.1016\/j.canlet.2026.218395_bib8","doi-asserted-by":"crossref","DOI":"10.1016\/j.clim.2025.110558","article-title":"Tumor-associated neutrophils: a complex role in cancer","volume":"280","author":"Gao","year":"2025","journal-title":"Clin Immunol"},{"issue":"21","key":"10.1016\/j.canlet.2026.218395_bib9","doi-asserted-by":"crossref","first-page":"5040","DOI":"10.1111\/febs.16730","article-title":"A guide to UFMylation, an emerging posttranslational modification","volume":"290","author":"Millrine","year":"2023","journal-title":"FEBS J."},{"issue":"1","key":"10.1016\/j.canlet.2026.218395_bib10","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.molcel.2023.11.034","article-title":"The UFM1 system: working principles, cellular functions, and pathophysiology","volume":"84","author":"Komatsu","year":"2024","journal-title":"Mol Cell."},{"issue":"1","key":"10.1016\/j.canlet.2026.218395_bib11","doi-asserted-by":"crossref","first-page":"7857","DOI":"10.1038\/s41467-022-35501-0","article-title":"The UFM1 system regulates ER-phagy through the ufmylation of CYB5R3","volume":"13","author":"Ishimura","year":"2022","journal-title":"Nat. Commun."},{"key":"10.1016\/j.canlet.2026.218395_bib12","doi-asserted-by":"crossref","DOI":"10.14218\/JCTH.2025.00318","article-title":"DysUFMylation of SREBP1 promotes the progression of hepatocellular carcinoma by reprogramming lipid metabolism","author":"Gao","year":"2025","journal-title":"J. Clin. Transl. Hepatol."},{"issue":"7","key":"10.1016\/j.canlet.2026.218395_bib13","doi-asserted-by":"crossref","first-page":"3031","DOI":"10.1002\/cam4.1591","article-title":"Low expression of WW domain-containing oxidoreductase associates with hepatocellular carcinoma aggressiveness and recurrence after curative resection","volume":"7","author":"Zhou","year":"2018","journal-title":"Cancer Med."},{"issue":"1","key":"10.1016\/j.canlet.2026.218395_bib14","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1055\/s-0030-1247132","article-title":"Modified RECIST (mRECIST) assessment for hepatocellular carcinoma","volume":"30","author":"Lencioni","year":"2010","journal-title":"Semin. Liver Dis."},{"issue":"8 Suppl","key":"10.1016\/j.canlet.2026.218395_bib15","first-page":"4244s","article-title":"Use of a monoclonal anti-estrogen receptor antibody in the immunohistochemical evaluation of human tumors","volume":"46","author":"McCarty","year":"1986","journal-title":"Cancer Res."},{"issue":"5","key":"10.1016\/j.canlet.2026.218395_bib16","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1002\/cyto.a.22271","article-title":"Normalization of mass cytometry data with bead standards","volume":"83","author":"Finck","year":"2013","journal-title":"Cytometry A"},{"issue":"3","key":"10.1016\/j.canlet.2026.218395_bib17","doi-asserted-by":"crossref","DOI":"10.1002\/jms.5116","article-title":"Mass spectrometry\u2013based proteomics in clinical diagnosis of amyloidosis and multiple myeloma: a review (2012\u20132024)","volume":"60","author":"Kratka","year":"2025","journal-title":"J. Mass Spectrom."},{"issue":"7938","key":"10.1016\/j.canlet.2026.218395_bib18","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/s41586-022-05400-x","article-title":"Liver tumour immune microenvironment subtypes and neutrophil heterogeneity","volume":"612","author":"Xue","year":"2022","journal-title":"Nature"},{"issue":"5","key":"10.1016\/j.canlet.2026.218395_bib19","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1038\/s41416-023-02552-z","article-title":"Tumor-associated neutrophils suppress CD8(+) T cell immunity in urothelial bladder carcinoma through the COX-2\/PGE2\/IDO1 Axis","volume":"130","author":"Ouyang","year":"2024","journal-title":"Br. J. Cancer"},{"key":"10.1016\/j.canlet.2026.218395_bib20","doi-asserted-by":"crossref","DOI":"10.1016\/j.canlet.2024.216903","article-title":"Acetyl-CoA metabolic accumulation promotes hepatocellular carcinoma metastasis via enhancing CXCL1-dependent infiltration of tumor-associated neutrophils","volume":"592","author":"Pan","year":"2024","journal-title":"Cancer Lett."},{"issue":"9","key":"10.1016\/j.canlet.2026.218395_bib21","doi-asserted-by":"crossref","first-page":"2274","DOI":"10.1002\/eji.202049029","article-title":"Differential Interleukin-8 thresholds for chemotaxis and netosis in human neutrophils","volume":"51","author":"Teijeira","year":"2021","journal-title":"Eur. J. Immunol."},{"issue":"4","key":"10.1016\/j.canlet.2026.218395_bib22","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1159\/000514885","article-title":"Interleukin 8 elicits rapid physiological changes in neutrophils that are altered by inflammatory conditions","volume":"13","author":"Bernhard","year":"2021","journal-title":"J. Innate Immun."},{"key":"10.1016\/j.canlet.2026.218395_bib23","first-page":"639","article-title":"N2 neutrophils and tumor progression in breast cancer: molecular pathways and implications","volume":"17","author":"Obeagu","year":"2025","journal-title":"Breast Cancer"},{"issue":"7","key":"10.1016\/j.canlet.2026.218395_bib24","first-page":"2060","article-title":"CXCL8 and its cognate receptors CXCR1\/CXCR2 in primary myelofibrosis","volume":"109","author":"Vermeersch","year":"2024","journal-title":"Haematologica"},{"key":"10.1016\/j.canlet.2026.218395_bib25","doi-asserted-by":"crossref","DOI":"10.3389\/fmolb.2022.723846","article-title":"CXCL8 in tumor biology and its implications for clinical translation","volume":"9","author":"Xiong","year":"2022","journal-title":"Front. Mol. Biosci."},{"issue":"6","key":"10.1016\/j.canlet.2026.218395_bib26","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.7150\/thno.15625","article-title":"Role of the CXCL8-CXCR1\/2 axis in cancer and inflammatory diseases","volume":"7","author":"Ha","year":"2017","journal-title":"Review. Theranostics."},{"issue":"9","key":"10.1016\/j.canlet.2026.218395_bib27","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1038\/nri887","article-title":"Nf-kappa B, chemokine gene transcription and tumour growth","volume":"2","author":"Richmond","year":"2002","journal-title":"Nat. Rev. Immunol."},{"issue":"1","key":"10.1016\/j.canlet.2026.218395_bib28","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1136\/gutjnl-2024-332998","article-title":"Identification of PRMT5 as a therapeutic target in cholangiocarcinoma","volume":"74","author":"Elurbide","year":"2024","journal-title":"Gut"},{"issue":"5","key":"10.1016\/j.canlet.2026.218395_bib29","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1002\/cac2.12284","article-title":"HSF1 facilitates the multistep process of lymphatic metastasis in bladder cancer via a novel PRMT5-WDR5-dependent transcriptional program","volume":"42","author":"Huang","year":"2022","journal-title":"Cancer Commun."},{"key":"10.1016\/j.canlet.2026.218395_bib30","doi-asserted-by":"crossref","DOI":"10.1016\/j.canlet.2024.217214","article-title":"Inhibition of PRMT5 moderately suppresses prostate cancer growth in vivo but enhances its response to immunotherapy","volume":"602","author":"He","year":"2024","journal-title":"Cancer Lett."},{"issue":"33","key":"10.1016\/j.canlet.2026.218395_bib31","doi-asserted-by":"crossref","first-page":"13516","DOI":"10.1073\/pnas.1311784110","article-title":"PRMT5 dimethylates R30 of the p65 subunit to activate NF-kappaB","volume":"110","author":"Wei","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"9","key":"10.1016\/j.canlet.2026.218395_bib32","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1038\/s41556-020-0559-z","article-title":"UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination","volume":"22","author":"Liu","year":"2020","journal-title":"Nat. Cell Biol."},{"issue":"7","key":"10.1016\/j.canlet.2026.218395_bib33","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1038\/s41419-024-06934-w","article-title":"Eg5 UFMylation promotes spindle organization during mitosis","volume":"15","author":"Li","year":"2024","journal-title":"Cell Death Dis."},{"issue":"2","key":"10.1016\/j.canlet.2026.218395_bib34","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.bbamcr.2015.12.001","article-title":"The E3 ubiquitin ligase CHIP mediates ubiquitination and proteasomal degradation of PRMT5","volume":"1863","author":"Zhang","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"issue":"7647","key":"10.1016\/j.canlet.2026.218395_bib35","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1038\/nature21676","article-title":"Effective combinatorial immunotherapy for castration-resistant prostate cancer","volume":"543","author":"Lu","year":"2017","journal-title":"Nature"},{"issue":"4","key":"10.1016\/j.canlet.2026.218395_bib36","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.ccell.2019.02.008","article-title":"KRAS-IRF2 axis drives immune suppression and immune therapy resistance in colorectal cancer","volume":"35","author":"Liao","year":"2019","journal-title":"Cancer Cell"},{"issue":"1","key":"10.1016\/j.canlet.2026.218395_bib37","first-page":"62","article-title":"Targeting T cell checkpoints 41BB and LAG3 and myeloid cell CXCR1\/CXCR2 results in antitumor immunity and durable response in pancreatic cancer","volume":"4","author":"Gulhati","year":"2023","journal-title":"Nat. Cancer"},{"issue":"6","key":"10.1016\/j.canlet.2026.218395_bib38","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1158\/1078-0432.CCR-19-2625","article-title":"Inhibition of MDSC trafficking with SX-682, a CXCR1\/2 inhibitor, enhances NK-Cell immunotherapy in head and neck cancer models","volume":"26","author":"Greene","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.canlet.2026.218395_bib39","doi-asserted-by":"crossref","DOI":"10.1016\/j.pharmthera.2020.107692","article-title":"Interleukin-8: a chemokine at the intersection of cancer plasticity, angiogenesis, and immune suppression","volume":"219","author":"Fousek","year":"2021","journal-title":"Pharmacol. Ther."},{"issue":"18","key":"10.1016\/j.canlet.2026.218395_bib40","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2322520121","article-title":"PARP1 UFMylation ensures the stability of stalled replication forks","volume":"121","author":"Gong","year":"2024","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"10","key":"10.1016\/j.canlet.2026.218395_bib41","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2025.116433","article-title":"Targeting the UFL1-PARP1 axis amplifies anti-tumor immunity","volume":"44","author":"Song","year":"2025","journal-title":"Cell Rep."},{"issue":"11","key":"10.1016\/j.canlet.2026.218395_bib42","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2215732120","article-title":"Dysregulation of PD-L1 by UFMylation imparts tumor immune evasion and identified as a potential therapeutic target","volume":"120","author":"Zhou","year":"2023","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"21","key":"10.1016\/j.canlet.2026.218395_bib43","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1056\/NEJMoa1501824","article-title":"Pembrolizumab for the treatment of non-small-cell lung cancer","volume":"372","author":"Garon","year":"2015","journal-title":"N. Engl. J. Med."},{"issue":"14","key":"10.1016\/j.canlet.2026.218395_bib44","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1056\/NEJMoa1917346","article-title":"Atezolizumab for first-line treatment of PD-L1-Selected patients with NSCLC","volume":"383","author":"Herbst","year":"2020","journal-title":"N. Engl. J. Med."},{"issue":"17","key":"10.1016\/j.canlet.2026.218395_bib45","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1056\/NEJMoa1507643","article-title":"Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer","volume":"373","author":"Borghaei","year":"2015","journal-title":"N. Engl. J. Med."},{"issue":"6","key":"10.1016\/j.canlet.2026.218395_bib46","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1016\/j.molcel.2024.01.024","article-title":"UFL1 ablation in T cells suppresses PD-1 UFMylation to enhance anti-tumor immunity","volume":"84","author":"He","year":"2024","journal-title":"Mol Cell"},{"issue":"3","key":"10.1016\/j.canlet.2026.218395_bib47","doi-asserted-by":"crossref","DOI":"10.3390\/cancers14030536","article-title":"The good, the bad, and the ugly: neutrophils, angiogenesis, and cancer","volume":"14","author":"Ozel","year":"2022","journal-title":"Cancers (Basel)"},{"key":"10.1016\/j.canlet.2026.218395_bib48","doi-asserted-by":"crossref","DOI":"10.1016\/j.canlet.2025.217692","article-title":"TRAIL induces cytokine production via the NFkB2 pathway promoting neutrophil chemotaxis and neutrophil-mediated immune-suppression in triple negative breast cancer cells","volume":"620","author":"Kundu","year":"2025","journal-title":"Cancer Lett."}],"container-title":["Cancer Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0304383526001588?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0304383526001588?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T12:12:50Z","timestamp":1777551170000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0304383526001588"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":48,"alternative-id":["S0304383526001588"],"URL":"https:\/\/doi.org\/10.1016\/j.canlet.2026.218395","relation":{},"ISSN":["0304-3835"],"issn-type":[{"value":"0304-3835","type":"print"}],"subject":[],"published":{"date-parts":[[2026,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"DysUFMylation reprograms immunosuppressive neutrophils to potentiate anti-PD-1 therapy in hepatocellular carcinoma","name":"articletitle","label":"Article Title"},{"value":"Cancer Letters","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.canlet.2026.218395","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"218395"}}