{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T16:59:01Z","timestamp":1785517141260,"version":"3.56.0"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":13,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Noncommunicable Chronic Diseases-National Science and Technology Major Project","award":["2024ZD0519700"],"award-info":[{"award-number":["2024ZD0519700"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"DOI":"10.1186\/s12967-026-08619-8","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T11:44:30Z","timestamp":1784115870000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Discovery of XNW5004 as a novel EZH2 inhibitor that enhances anti-tumor immunity and synergizes with PD-1 blockade immunotherapy in lung adenocarcinoma"],"prefix":"10.1186","volume":"24","author":[{"given":"Zhihuan","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjuan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haishuang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxian","family":"Sima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"8619_CR1","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/j.phrs.2015.06.011","volume":"99","author":"A Bobbio","year":"2015","unstructured":"Bobbio A, Alifano M. Immune therapy of non-small cell lung cancer. The future. Pharmacol Res. 2015;99:217\u201322.","journal-title":"Pharmacol Res"},{"key":"8619_CR2","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1056\/NEJMoa1507643","volume":"373","author":"H Borghaei","year":"2015","unstructured":"Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, et al. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med. 2015;373:1627\u201339.","journal-title":"N Engl J Med"},{"key":"8619_CR3","doi-asserted-by":"publisher","first-page":"1819","DOI":"10.1016\/S0140-6736(18)32409-7","volume":"393","author":"TSK Mok","year":"2019","unstructured":"Mok TSK, Wu YL, Kudaba I, Kowalski DM, Cho BC, Turna HZ, Castro G Jr., Srimuninnimit V, Laktionov KK, Bondarenko I, et al. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet. 2019;393:1819\u201330.","journal-title":"Lancet"},{"key":"8619_CR4","doi-asserted-by":"publisher","first-page":"8295","DOI":"10.1073\/pnas.1819029116","volume":"116","author":"KS Jani","year":"2019","unstructured":"Jani KS, Jain SU, Ge EJ, Diehl KL, Lundgren SM, Muller MM, Lewis PW, Muir TW. Histone H3 tail binds a unique sensing pocket in EZH2 to activate the PRC2 methyltransferase. Proc Natl Acad Sci U S A. 2019;116:8295\u2013300.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"8619_CR5","doi-asserted-by":"publisher","first-page":"1525","DOI":"10.1093\/carcin\/bgr171","volume":"32","author":"SR Choudhury","year":"2011","unstructured":"Choudhury SR, Balasubramanian S, Chew YC, Han B, Marquez VE, Eckert RL. (-)-Epigallocatechin-3-gallate and DZNep reduce polycomb protein level via a proteasome-dependent mechanism in skin cancer cells. Carcinogenesis. 2011;32:1525\u201332.","journal-title":"Carcinogenesis"},{"key":"8619_CR6","doi-asserted-by":"crossref","unstructured":"Luo L, Wang Z, Hu T, Feng Z, Zeng Q, Shu X, Wu A, Huang P, Cao Y, Tu Y, Li Z. Multiomics characteristics and immunotherapeutic potential of EZH2 in pan-cancer. Biosci Rep. 2023;43: BSR20222230 .","DOI":"10.1042\/BSR20222230"},{"key":"8619_CR7","doi-asserted-by":"publisher","first-page":"1599","DOI":"10.1002\/cncr.26441","volume":"118","author":"R Huqun, Ishikawa","year":"2012","unstructured":"Huqun, Ishikawa R, Zhang J, Miyazawa H, Goto Y, Shimizu Y, Hagiwara K, Koyama N. Enhancer of zeste homolog 2 is a novel prognostic biomarker in nonsmall cell lung cancer. Cancer. 2012;118:1599\u2013606.","journal-title":"Cancer"},{"key":"8619_CR8","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1038\/labinvest.2008.52","volume":"88","author":"M Sasaki","year":"2008","unstructured":"Sasaki M, Ikeda H, Itatsu K, Yamaguchi J, Sawada S, Minato H, Ohta T, Nakanuma Y. The overexpression of polycomb group proteins Bmi1 and EZH2 is associated with the progression and aggressive biological behavior of hepatocellular carcinoma. Lab Invest. 2008;88:873\u201382.","journal-title":"Lab Invest"},{"key":"8619_CR9","doi-asserted-by":"publisher","first-page":"5878","DOI":"10.1038\/s41467-020-19704-x","volume":"11","author":"Y Bao","year":"2020","unstructured":"Bao Y, Oguz G, Lee WC, Lee PL, Ghosh K, Li J, Wang P, Lobie PE, Ehmsen S, Ditzel HJ, et al. EZH2-mediated PP2A inactivation confers resistance to HER2-targeted breast cancer therapy. Nat Commun. 2020;11:5878.","journal-title":"Nat Commun"},{"key":"8619_CR10","doi-asserted-by":"crossref","unstructured":"Wang Z, Guo Z, Wang X, Liao H, Chai Y, Wang Z, Wang Z. Inhibition of EZH2 ameliorates sepsis acute lung injury (SALI) and non-small-cell lung cancer (NSCLC) proliferation through the PD-L1 pathway. Cells. 2022;11:3958.","DOI":"10.3390\/cells11243958"},{"key":"8619_CR11","doi-asserted-by":"publisher","first-page":"2296","DOI":"10.1182\/blood-2022-166991","volume":"140","author":"CL Batlevi","year":"2022","unstructured":"Batlevi CL, Salles G, Park SI, Phillips TJ, Amengual JE, Andorsky D, Campbell P, McKay P, Leonard JP, Sondhi M, et al. Tazemetostat in Combination with Lenalidomide and Rituximab in Patients with Relapsed\/Refractory Follicular Lymphoma: Phase 1b Results of Symphony-1. Blood. 2022;140:2296\u20138.","journal-title":"Blood"},{"key":"8619_CR12","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1038\/s41392-024-02039-0","volume":"9","author":"W Dai","year":"2024","unstructured":"Dai W, Qiao X, Fang Y, Guo R, Bai P, Liu S, Li T, Jiang Y, Wei S, Na Z, et al. Epigenetics-targeted drugs: current paradigms and future challenges. Signal Transduct Target Ther. 2024;9:332.","journal-title":"Signal Transduct Target Ther"},{"key":"8619_CR13","doi-asserted-by":"publisher","first-page":"9353","DOI":"10.1182\/blood-2022-157853","volume":"140","author":"Z Weiwei","year":"2022","unstructured":"Weiwei Z, Hui Z, Zhang X, Hongmei J, Dongmei Z, Fang Z, Li G, Wei W, Yaobo S, Yan H, et al. An Open-Label, Multicenter,Single-Arm, Phase I Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics and Efficacy of XNW5004 in Patients with Relapsed or Refractory Hematologic Malignancies. Blood. 2022;140:9353\u20135.","journal-title":"Blood"},{"key":"8619_CR14","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1200\/JCO.2026.44.7_suppl.169","volume":"44","author":"Y Chang","year":"2026","unstructured":"Chang Y, Zhang J, Niu H, Bian J, Jiang S, Liang C, Li Y, Guo H, Xing J, Shi Z, et al. A phase 1b\/2 study to evaluate the safety and efficacy of igermetostat (XNW5004) in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer. J Clin Oncol. 2026;44:169\u2013169.","journal-title":"J Clin Oncol"},{"key":"8619_CR15","doi-asserted-by":"publisher","first-page":"3089","DOI":"10.1158\/1538-7445.AM2023-3089","volume":"83","author":"Y Hu","year":"2023","unstructured":"Hu Y, Peng W, Zhang Z, Wu Z, Chen X, Huang Y, Li X, Liu C, Liu X, Shi Q, et al. Abstract 3089: XNW5004: a novel EZH2 inhibitor efficacious in multiple cancer xenograft models as a single agent and in combination studies. Cancer Res. 2023;83:3089\u20133089.","journal-title":"Cancer Res"},{"key":"8619_CR16","doi-asserted-by":"publisher","first-page":"612397","DOI":"10.3389\/fnut.2020.612397","volume":"7","author":"Y Deng","year":"2020","unstructured":"Deng Y, Govers C, Ter Beest E, van Dijk AJ, Hettinga K, Wichers HJ. A THP-1 Cell Line-Based Exploration of Immune Responses Toward Heat-Treated BLG. Front Nutr. 2020;7:612397.","journal-title":"Front Nutr"},{"key":"8619_CR17","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1016\/j.foodchem.2012.10.076","volume":"138","author":"S Katayama","year":"2013","unstructured":"Katayama S, Kukita T, Ishikawa E, Nakashima S, Masuda S, Kanda T, Akiyama H, Teshima R, Nakamura S. Apple polyphenols suppress antigen presentation of ovalbumin by THP-1-derived dendritic cells. Food Chem. 2013;138:757\u201361.","journal-title":"Food Chem"},{"key":"8619_CR18","doi-asserted-by":"publisher","first-page":"2109","DOI":"10.1016\/j.jtho.2021.07.015","volume":"16","author":"Y Yang","year":"2021","unstructured":"Yang Y, Sun J, Wang Z, Fang J, Yu Q, Han B, Cang S, Chen G, Mei X, Yang Z, et al. Updated Overall Survival Data and Predictive Biomarkers of Sintilimab Plus Pemetrexed and Platinum as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC in the Phase 3 ORIENT-11 Study. J Thorac Oncol. 2021;16:2109\u201320.","journal-title":"J Thorac Oncol"},{"key":"8619_CR19","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1007\/s40265-020-01288-x","volume":"80","author":"SM Hoy","year":"2020","unstructured":"Hoy SM. Tazemetostat: First Approval. Drugs. 2020;80:513\u201321.","journal-title":"Drugs"},{"key":"8619_CR20","doi-asserted-by":"publisher","first-page":"11003","DOI":"10.1200\/JCO.2019.37.15_suppl.11003","volume":"37","author":"S Stacchiotti","year":"2019","unstructured":"Stacchiotti S, Schoffski P, Jones R, Agulnik M, Villalobos VM, Jahan TM, Chen TW-W, Italiano A, Demetri GD, Cote GM, et al. Safety and efficacy of tazemetostat, a first-in-class EZH2 inhibitor, in patients (pts) with epithelioid sarcoma (ES) (NCT02601950). J Clin Oncol. 2019;37:11003\u201311003.","journal-title":"J Clin Oncol"},{"key":"8619_CR21","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/j.cell.2018.08.058","volume":"175","author":"X Huang","year":"2018","unstructured":"Huang X, Yan J, Zhang M, Wang Y, Chen Y, Fu X, Wei R, Zheng XL, Liu Z, Zhang X, et al. Targeting Epigenetic Crosstalk as a Therapeutic Strategy for EZH2-Aberrant Solid Tumors. Cell. 2018;175:186\u201399. e119.","journal-title":"Cell"},{"key":"8619_CR22","unstructured":"IPSEN. Ipsen voluntarily withdraws Tazverik\u00ae (tazemetostat) in follicular lymphoma and epithelioid sarcoma. 2026."},{"key":"8619_CR23","unstructured":"Administration USFaD. FDA alerts health care providers and patients about increased risk of new blood cancers with Tazverik (tazemetostat) use; sponsor to voluntarily withdraw product from market. 2026."},{"key":"8619_CR24","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1016\/S1470-2045(18)30149-9","volume":"19","author":"S Makita","year":"2018","unstructured":"Makita S, Tobinai K. Targeting EZH2 with tazemetostat. Lancet Oncol. 2018;19:586\u20137.","journal-title":"Lancet Oncol"},{"key":"8619_CR25","doi-asserted-by":"publisher","first-page":"116624","DOI":"10.1016\/j.biopha.2024.116624","volume":"175","author":"Y Chen","year":"2024","unstructured":"Chen Y, Zhu H, Luo Y, Tong S, Liu Y. EZH2: The roles in targeted therapy and mechanisms of resistance in breast cancer. Biomed Pharmacother. 2024;175:116624.","journal-title":"Biomed Pharmacother"},{"key":"8619_CR26","doi-asserted-by":"publisher","first-page":"7012","DOI":"10.1200\/JCO.2025.43.16_suppl.7012","volume":"43","author":"L Qiu","year":"2025","unstructured":"Qiu L, Qi J, Zheng W, Qian Z, Zhou K-S, Cai Q, Zhong K, Jing H, Wu J, Xing X, et al. A phase 1\/2 study to evaluate the safety and efficacy of XNW5004, a selective EZH2 inhibitor, in subjects with relapsed\/refractory non-Hodgkin lymphoma. J Clin Oncol. 2025;43:7012\u20137012.","journal-title":"J Clin Oncol"},{"key":"8619_CR27","doi-asserted-by":"publisher","first-page":"107905","DOI":"10.1016\/j.celrep.2020.107905","volume":"32","author":"P Kozik","year":"2020","unstructured":"Kozik P, Gros M, Itzhak DN, Joannas L, Heurtebise-Chr\u00e9tien S, Krawczyk PA, Rodr\u00edguez-Silvestre P, Alloatti A, Magalhaes JG, Del Nery E, et al. Small Molecule Enhancers of Endosome-to-Cytosol Import Augment Anti-tumor Immunity. Cell Rep. 2020;32:107905.","journal-title":"Cell Rep"},{"key":"8619_CR28","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1186\/s12943-022-01656-z","volume":"21","author":"RJ Daly","year":"2022","unstructured":"Daly RJ, Scott AM, Klein O, Ernst M. Enhancing therapeutic anti-cancer responses by combining immune checkpoint and tyrosine kinase inhibition. Mol Cancer. 2022;21:189.","journal-title":"Mol Cancer"},{"key":"8619_CR29","doi-asserted-by":"publisher","first-page":"636568","DOI":"10.3389\/fimmu.2021.636568","volume":"12","author":"K Dhatchinamoorthy","year":"2021","unstructured":"Dhatchinamoorthy K, Colbert JD, Rock KL. Cancer Immune Evasion Through Loss of MHC Class I Antigen Presentation. Front Immunol. 2021;12:636568.","journal-title":"Front Immunol"},{"key":"8619_CR30","doi-asserted-by":"publisher","first-page":"844866","DOI":"10.3389\/fimmu.2022.844866","volume":"13","author":"BC Taylor","year":"2022","unstructured":"Taylor BC, Balko JM. Mechanisms of MHC-I Downregulation and Role in Immunotherapy Response. Front Immunol. 2022;13:844866.","journal-title":"Front Immunol"},{"key":"8619_CR31","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1158\/2159-8290.CD-18-1090","volume":"9","author":"D Ennishi","year":"2019","unstructured":"Ennishi D, Takata K, Beguelin W, Duns G, Mottok A, Farinha P, Bashashati A, Saberi S, Boyle M, Meissner B, et al. Molecular and Genetic Characterization of MHC Deficiency Identifies EZH2 as Therapeutic Target for Enhancing Immune Recognition. Cancer Discov. 2019;9:546\u201363.","journal-title":"Cancer Discov"},{"key":"8619_CR32","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1158\/1078-0432.CCR-19-1351","volume":"26","author":"L Zhou","year":"2020","unstructured":"Zhou L, Mudianto T, Ma X, Riley R, Uppaluri R. Targeting EZH2 Enhances Antigen Presentation, Antitumor Immunity, and Circumvents Anti-PD-1 Resistance in Head and Neck Cancer. Clin Cancer Res. 2020;26:290\u2013300.","journal-title":"Clin Cancer Res"},{"key":"8619_CR33","doi-asserted-by":"publisher","first-page":"101313","DOI":"10.1016\/j.gendis.2024.101313","volume":"12","author":"M Xu","year":"2025","unstructured":"Xu M, Xu C, Wang R, Tang Q, Zhou Q, Wu W, Wan X, Mo H, Pan J, Wang S. Treating human cancer by targeting EZH2. Genes Dis. 2025;12:101313.","journal-title":"Genes Dis"},{"key":"8619_CR34","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1186\/s40425-019-0784-9","volume":"7","author":"G Xiao","year":"2019","unstructured":"Xiao G, Jin LL, Liu CQ, Wang YC, Meng YM, Zhou ZG, Chen J, Yu XJ, Zhang YJ, Xu J, Zheng L. EZH2 negatively regulates PD-L1 expression in hepatocellular carcinoma. J Immunother Cancer. 2019;7:300.","journal-title":"J Immunother Cancer"},{"key":"8619_CR35","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.bbrc.2019.07.039","volume":"517","author":"Y Zhao","year":"2019","unstructured":"Zhao Y, Wang XX, Wu W, Long H, Huang J, Wang Z, Li T, Tang S, Zhu B, Chen D. EZH2 regulates PD-L1 expression via HIF-1alpha in non-small cell lung cancer cells. Biochem Biophys Res Commun. 2019;517:201\u20139.","journal-title":"Biochem Biophys Res Commun"},{"key":"8619_CR36","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1002\/JLB.2MR0220-549R","volume":"108","author":"TM Bui","year":"2020","unstructured":"Bui TM, Wiesolek HL, Sumagin R. ICAM-1: A master regulator of cellular responses in inflammation, injury resolution, and tumorigenesis. J Leukoc Biol. 2020;108:787\u201399.","journal-title":"J Leukoc Biol"},{"key":"8619_CR37","doi-asserted-by":"publisher","first-page":"3259","DOI":"10.4049\/jimmunol.160.7.3259","volume":"160","author":"LA Zuckerman","year":"1998","unstructured":"Zuckerman LA, Pullen L, Miller J. Functional consequences of costimulation by ICAM-1 on IL-2 gene expression and T cell activation. J Immunol. 1998;160:3259\u201368.","journal-title":"J Immunol"},{"key":"8619_CR38","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1158\/2326-6066.CIR-15-0146","volume":"4","author":"FS Basingab","year":"2016","unstructured":"Basingab FS, Ahmadi M, Morgan DJ. IFNgamma-Dependent Interactions between ICAM-1 and LFA-1 Counteract Prostaglandin E2-Mediated Inhibition of Antitumor CTL Responses. Cancer Immunol Res. 2016;4:400\u201311.","journal-title":"Cancer Immunol Res"},{"key":"8619_CR39","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1002\/ijc.10514","volume":"100","author":"Y Maruo","year":"2002","unstructured":"Maruo Y, Gochi A, Kaihara A, Shimamura H, Yamada T, Tanaka N, Orita K. ICAM-1 expression and the soluble ICAM-1 level for evaluating the metastatic potential of gastric cancer. Int J Cancer. 2002;100:486\u201390.","journal-title":"Int J Cancer"},{"key":"8619_CR40","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1038\/mt.2014.215","volume":"23","author":"T Straetemans","year":"2015","unstructured":"Straetemans T, Berrevoets C, Coccoris M, Treffers-Westerlaken E, Wijers R, Cole DK, Dardalhon V, Sewell AK, Taylor N, Verweij J, Debets R. Recurrence of melanoma following T cell treatment: continued antigen expression in a tumor that evades T cell recruitment. Mol Ther. 2015;23:396\u2013406.","journal-title":"Mol Ther"},{"key":"8619_CR41","doi-asserted-by":"crossref","unstructured":"Almowallad S, Huwait E, Al-Massabi R, Saddeek S, Gauthaman K, Prola A. Punicalagin regulates key processes associated with atherosclerosis in THP-1 cellular model. Pharmaceuticals (Basel). 2020;13:372.","DOI":"10.3390\/ph13110372"},{"key":"8619_CR42","doi-asserted-by":"publisher","first-page":"e24988","DOI":"10.1016\/j.heliyon.2024.e24988","volume":"10","author":"Z Fang","year":"2024","unstructured":"Fang Z, Xue Y, Leng Y, Zhang L, Ren X, Yang N, Chen J, Chen L, Wang H. Erzhi pills reverse PD-L1-mediated immunosuppression in melanoma microenvironment. Heliyon. 2024;10:e24988.","journal-title":"Heliyon"},{"key":"8619_CR43","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1186\/s12985-020-01341-x","volume":"17","author":"Q Zhang","year":"2020","unstructured":"Zhang Q, Mu X, Dong H, Hu G, Zhang T, He C, Siddique N. Pulmonary endothelium-derived PD-L1 induced by the H9N2 avian influenza virus inhibits the immune response of T cells. Virol J. 2020;17:92.","journal-title":"Virol J"},{"key":"8619_CR44","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1186\/s12885-022-09169-0","volume":"22","author":"ALB Bennedsen","year":"2022","unstructured":"Bennedsen ALB, Cai L, Hasselager RP, \u00d6zcan AA, Mohamed KB, Eriksen JO, Eiholm S, Bzorek M, Fiehn AK, Hviid TVF, G\u00f6genur I. An exploration of immunohistochemistry-based prognostic markers in patients undergoing curative resections for colon cancer. BMC Cancer. 2022;22:62.","journal-title":"BMC Cancer"},{"key":"8619_CR45","doi-asserted-by":"crossref","unstructured":"Choi EJ, Jeon CH, Lee IK. Ferric ammonium citrate upregulates PD-L1 expression through generation of reactive oxygen species. J Immunol Res. 2022;2022:6284124.","DOI":"10.1155\/2022\/6284124"},{"key":"8619_CR46","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1038\/nature07317","volume":"455","author":"H Ishikawa","year":"2008","unstructured":"Ishikawa H, Barber GN. STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature. 2008;455:674\u20138.","journal-title":"Nature"},{"key":"8619_CR47","doi-asserted-by":"publisher","first-page":"105514","DOI":"10.1016\/j.phrs.2021.105514","volume":"166","author":"SS Zou","year":"2021","unstructured":"Zou SS, Qiao Y, Zhu S, Gao B, Yang N, Liu YJ, Chen J. Intrinsic strategies for the evasion of cGAS-STING signaling-mediated immune surveillance in human cancer: How therapy can overcome them. Pharmacol Res. 2021;166:105514.","journal-title":"Pharmacol Res"},{"key":"8619_CR48","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1038\/s41556-025-01627-8","volume":"27","author":"Y Duan","year":"2025","unstructured":"Duan Y, Hu Z, Han P, Lei B, Wang S, Wang Z, Hou Y, Lin Y, Li M, Xiao L, et al. ADSL-generated fumarate binds and inhibits STING to promote tumour immune evasion. Nat Cell Biol. 2025;27:668\u201382.","journal-title":"Nat Cell Biol"},{"key":"8619_CR49","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1016\/j.molcel.2008.11.004","volume":"32","author":"R Margueron","year":"2008","unstructured":"Margueron R, Li G, Sarma K, Blais A, Zavadil J, Woodcock CL, Dynlacht BD, Reinberg D. Ezh1 and Ezh2 maintain repressive chromatin through different mechanisms. Mol Cell. 2008;32:503\u201318.","journal-title":"Mol Cell"},{"key":"8619_CR50","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1038\/nature23449","volume":"548","author":"KJ Mackenzie","year":"2017","unstructured":"Mackenzie KJ, Carroll P, Martin CA, Murina O, Fluteau A, Simpson DJ, Olova N, Sutcliffe H, Rainger JK, Leitch A, et al. cGAS surveillance of micronuclei links genome instability to innate immunity. Nature. 2017;548:461\u20135.","journal-title":"Nature"},{"key":"8619_CR51","doi-asserted-by":"publisher","first-page":"1758","DOI":"10.1016\/j.ymthe.2021.02.005","volume":"29","author":"J Lai","year":"2021","unstructured":"Lai J, Fu Y, Tian S, Huang S, Luo X, Lin L, Zhang X, Wang H, Lin Z, Zhao H, et al. Zebularine elevates STING expression and enhances cGAMP cancer immunotherapy in mice. Mol Ther. 2021;29:1758\u201371.","journal-title":"Mol Ther"},{"key":"8619_CR52","doi-asserted-by":"publisher","first-page":"e2006134","DOI":"10.1371\/journal.pbio.2006134","volume":"16","author":"L Wu","year":"2018","unstructured":"Wu L, Cao J, Cai WL, Lang SM, Horton JR, Jansen DJ, Liu ZZ, Chen JF, Zhang M, Mott BT, et al. KDM5 histone demethylases repress immune response via suppression of STING. PLoS Biol. 2018;16:e2006134.","journal-title":"PLoS Biol"},{"key":"8619_CR53","doi-asserted-by":"crossref","unstructured":"Lalle G, Twardowski J, Grinberg-Bleyer Y. NF-kappaB in cancer immunity: friend or foe? Cells. 2021;10.","DOI":"10.3390\/cells10020355"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12967-026-08619-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-026-08619-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-026-08619-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T16:03:04Z","timestamp":1785513784000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12967-026-08619-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,15]]},"references-count":53,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["8619"],"URL":"https:\/\/doi.org\/10.1186\/s12967-026-08619-8","relation":{},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,15]]},"assertion":[{"value":"23 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All mouse experiments were approved by the Institutional Animal Care and Use Committee of Sun Yat-sen University Cancer Center (Ethics approval number: L102042021040S). The use of. human samples was approved by the Ethics Committee of Sun Yat-sen University Cancer Center (Ethics approval number: A2018-025-01).","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"968"}}