{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T14:26:06Z","timestamp":1788445566061,"version":"build-2803163510"},"reference-count":48,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["3332024048"],"award-info":[{"award-number":["3332024048"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018904","name":"Beijing Xisike Clinical Oncology Research Foundation","doi-asserted-by":"publisher","award":["Y-Young2024-0346"],"award-info":[{"award-number":["Y-Young2024-0346"]}],"id":[{"id":"10.13039\/100018904","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014717","name":"Youth Science Fund Project","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014717","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82202992"],"award-info":[{"award-number":["82202992"]}],"id":[{"id":"10.13039\/501100001809","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":[[2026,3]]},"DOI":"10.1016\/j.canlet.2026.218259","type":"journal-article","created":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T23:17:02Z","timestamp":1768691822000},"page":"218259","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"special_numbering":"C","title":["IL-6 drives chemoimmunotherapy resistance in NSCLC by reprogramming myeloid cells and impairing cytotoxic lymphocyte function"],"prefix":"10.1016","volume":"641","author":[{"given":"Yaning","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengming","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4286-9586","authenticated-orcid":false,"given":"Lu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sufei","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linyan","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1743-6383","authenticated-orcid":false,"given":"Yan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.canlet.2026.218259_bib1","first-page":"12","article-title":"Cancer statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"10.1016\/j.canlet.2026.218259_bib2","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1200\/JCO.22.01990","article-title":"Pembrolizumab plus chemotherapy in squamous non\u2013small-cell lung cancer: 5-year update of the phase III KEYNOTE-407 study","volume":"41","author":"Novello","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.canlet.2026.218259_bib3","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1056\/NEJMoa1801005","article-title":"Pembrolizumab plus chemotherapy in metastatic non\u2013small-cell lung cancer","volume":"378","author":"Gandhi","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.canlet.2026.218259_bib4","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/S1470-2045(21)00650-1","article-title":"Sugemalimab versus placebo, in combination with platinum-based chemotherapy, as first-line treatment of metastatic non-small-cell lung cancer (GEMSTONE-302): interim and final analyses of a double-blind, randomised, phase 3 clinical trial","volume":"23","author":"Zhou","year":"2022","journal-title":"Lancet Oncol."},{"key":"10.1016\/j.canlet.2026.218259_bib5","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1200\/JCO.18.00149","article-title":"Updated analysis of KEYNOTE-024: pembrolizumab versus platinum-based chemotherapy for advanced non\u2013small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater","volume":"37","author":"Reck","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.canlet.2026.218259_bib6","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1056\/NEJMoa1606774","article-title":"Pembrolizumab versus chemotherapy for PD-L1\u2013positive non\u2013small-cell lung cancer","volume":"375","author":"Reck","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.canlet.2026.218259_bib7","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1186\/s40425-019-0768-9","article-title":"The role of PD-L1 expression as a predictive biomarker: an analysis of all US Food and Drug Administration (FDA) approvals of immune checkpoint inhibitors","volume":"7","author":"Davis","year":"2019","journal-title":"J. Immunother. Cancer"},{"key":"10.1016\/j.canlet.2026.218259_bib8","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1089\/jir.2018.0019","article-title":"Cytokines in the treatment of cancer","volume":"39","author":"Conlon","year":"2019","journal-title":"J. Interferon Cytokine Res."},{"key":"10.1016\/j.canlet.2026.218259_bib9","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1111\/j.1525-1594.1996.tb04529.x","article-title":"Molecular biology of cytokines","volume":"20","author":"Dendorfer","year":"1996","journal-title":"Artif. Organs"},{"key":"10.1016\/j.canlet.2026.218259_bib10","doi-asserted-by":"crossref","first-page":"S34","DOI":"10.1002\/eji.200737772","article-title":"Historical insights into cytokines","volume":"37","author":"Dinarello","year":"2007","journal-title":"Eur. J. Immunol."},{"key":"10.1016\/j.canlet.2026.218259_bib11","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a028472","article-title":"Cytokines in cancer immunotherapy","volume":"10","author":"Waldmann","year":"2018","journal-title":"Cold Spring Harbor Perspect. Biol."},{"key":"10.1016\/j.canlet.2026.218259_bib12","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2023-007530","article-title":"New perspectives in cancer immunotherapy: targeting IL-6 cytokine family","volume":"11","author":"Soler","year":"2023","journal-title":"J. Immunother. Cancer"},{"key":"10.1016\/j.canlet.2026.218259_bib13","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/nature07205","article-title":"Cancer-related inflammation","volume":"454","author":"Mantovani","year":"2008","journal-title":"nature"},{"issue":"11","key":"10.1016\/j.canlet.2026.218259_bib14","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/j.tem.2023.08.001","article-title":"The exercise IL-6 enigma in cancer","volume":"34","author":"Orange","year":"2023","journal-title":"Trends Endocrinol. Metabol."},{"issue":"5","key":"10.1016\/j.canlet.2026.218259_bib15","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/ni.3153","article-title":"IL-6 as a keystone cytokine in health and disease","volume":"16","author":"Hunter","year":"2015","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.canlet.2026.218259_bib16","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1186\/s12916-022-02356-7","article-title":"Systematic analysis of IL-6 as a predictive biomarker and desensitizer of immunotherapy responses in patients with non-small cell lung cancer","volume":"20","author":"Liu","year":"2022","journal-title":"BMC Med."},{"key":"10.1016\/j.canlet.2026.218259_bib17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10238-025-01587-1","article-title":"Predictive value of serum cytokines in patients with non-small-cell lung cancer receiving anti-PD-1 blockade therapy: a meta-analysis","volume":"25","author":"Liu","year":"2025","journal-title":"Clin. Exp. Med."},{"key":"10.1016\/j.canlet.2026.218259_bib18","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1111\/1759-7714.14248","article-title":"Circulating cytokines associated with clinical outcomes in advanced non-small cell lung cancer patients who received chemoimmunotherapy","volume":"13","author":"Shi","year":"2022","journal-title":"Thorac. Cancer"},{"key":"10.1016\/j.canlet.2026.218259_bib19","article-title":"Plasma levels of 12 different cytokines correlate to PD-1 inhibitor combined chemotherapy responses in advanced non-small-cell lung cancer patient","volume":"124","author":"Peng","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.canlet.2026.218259_bib20","article-title":"CD8+ T cell-intrinsic IL-6 signaling promotes resistance to anti-PD-L1 immunotherapy","volume":"4","author":"Huseni","year":"2023","journal-title":"Cell Rep. Med."},{"key":"10.1016\/j.canlet.2026.218259_bib21","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1136\/gutjnl-2016-311585","article-title":"IL-6 and PD-L1 antibody blockade combination therapy reduces tumour progression in murine models of pancreatic cancer","volume":"67","author":"Mace","year":"2018","journal-title":"Gut"},{"key":"10.1016\/j.canlet.2026.218259_bib22","doi-asserted-by":"crossref","first-page":"e16","DOI":"10.1093\/nar\/gky1173","article-title":"scFTD-seq: freeze-thaw lysis based, portable approach toward highly distributed single-cell 3' mRNA profiling","volume":"47","author":"B","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.canlet.2026.218259_bib23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13059-017-1382-0","article-title":"SCANPY: large-scale single-cell gene expression data analysis","volume":"19","author":"Wolf","year":"2018","journal-title":"Genome Biol."},{"key":"10.1016\/j.canlet.2026.218259_bib24","article-title":"Gene signature extraction and cell identity recognition at the single-cell level with Cell-ID","volume":"1\u20138","author":"Cortal","year":"2021","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.canlet.2026.218259_bib25","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: an R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS A J. Integr. Biol."},{"key":"10.1016\/j.canlet.2026.218259_bib26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2105-14-7","article-title":"GSVA: gene set variation analysis for microarray and RNA-seq data","volume":"14","author":"H\u00e4nzelmann","year":"2013","journal-title":"BMC Bioinf."},{"key":"10.1016\/j.canlet.2026.218259_bib27","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2020-000842","article-title":"Serum interleukin-6 and C-reactive protein are associated with survival in melanoma patients receiving immune checkpoint inhibition","volume":"8","author":"Laino","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"10.1016\/j.canlet.2026.218259_bib28","doi-asserted-by":"crossref","DOI":"10.1016\/j.canlet.2025.217620","article-title":"Irreversible electroporation combined with PD-L1\/IL-6 dual blockade promotes anti-tumor immunity via cDC 2\/CD4+T cell axis in MHC-I deficient pancreatic cancer","volume":"617","author":"Wu","year":"2025","journal-title":"Cancer Lett."},{"key":"10.1016\/j.canlet.2026.218259_bib29","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.1007\/s00262-023-03453-z","article-title":"Cytokine profiling identifies circulating IL-6 and IL-15 as prognostic stratifiers in patients with non-small cell lung cancer receiving anti-PD-1\/PD-L1 blockade therapy","volume":"72","author":"Inoue","year":"2023","journal-title":"Cancer Immunol. Immunother."},{"key":"10.1016\/j.canlet.2026.218259_bib30","article-title":"Prognostic role of serum cytokines level in non-small cell lung cancer patients with anti-PD-1 and chemotherapy combined treatment","volume":"15","author":"Liu","year":"2024","journal-title":"Front. Immunol."},{"key":"10.1016\/j.canlet.2026.218259_bib31","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1158\/2326-6066.CIR-13-0030","article-title":"Myeloid-derived suppressor cells attenuate TH1 development through IL-6 production to promote tumor progression","volume":"1","author":"Tsukamoto","year":"2013","journal-title":"Cancer Immunol. Res."},{"key":"10.1016\/j.canlet.2026.218259_bib32","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s00262-015-1791-4","article-title":"IL-6 down-regulates HLA class II expression and IL-12 production of human dendritic cells to impair activation of antigen-specific CD4+ T cells","volume":"65","author":"Ohno","year":"2016","journal-title":"Cancer Immunol. Immunother."},{"key":"10.1016\/j.canlet.2026.218259_bib33","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1111\/cas.13330","article-title":"Lack of interleukin\u20106 in the tumor microenvironment augments type\u20101 immunity and increases the efficacy of cancer immunotherapy","volume":"108","author":"Ohno","year":"2017","journal-title":"Cancer Sci."},{"key":"10.1016\/j.canlet.2026.218259_bib34","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1111\/cas.13332","article-title":"Interleukin\u20106\/STAT 3 signaling as a promising target to improve the efficacy of cancer immunotherapy","volume":"108","author":"Kitamura","year":"2017","journal-title":"Cancer Sci."},{"key":"10.1016\/j.canlet.2026.218259_bib35","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1111\/cas.13433","article-title":"Immune\u2010suppressive effects of interleukin\u20106 on t\u2010cell\u2010mediated anti\u2010tumor immunity","volume":"109","author":"Tsukamoto","year":"2018","journal-title":"Cancer Sci."},{"key":"10.1016\/j.canlet.2026.218259_bib36","article-title":"CD8+ T cell-intrinsic IL-6 signaling promotes resistance to anti-PD-L1 immunotherapy","volume":"4","author":"Huseni","year":"2023","journal-title":"Cell Rep. Med."},{"key":"10.1016\/j.canlet.2026.218259_bib37","doi-asserted-by":"crossref","first-page":"4029","DOI":"10.1200\/JCO.23.02747","article-title":"Phase III KEYNOTE-789 Study of pemetrexed and platinum with or without pembrolizumab for tyrosine kinase Inhibitor\u2012Resistant, EGFR\u2013Mutant, metastatic nonsquamous non\u2013small cell lung cancer","volume":"42","author":"Yang","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.canlet.2026.218259_bib38","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.canlet.2019.10.027","article-title":"The superior efficacy of anti-PD-1\/PD-L1 immunotherapy in KRAS-mutant non-small cell lung cancer that correlates with an inflammatory phenotype and increased immunogenicity","volume":"470","author":"Liu","year":"2020","journal-title":"Cancer Lett."},{"key":"10.1016\/j.canlet.2026.218259_bib39","first-page":"21","article-title":"Tumor microenvironment-driven resistance to immunotherapy in non-small cell lung cancer: strategies for cold-to-hot tumor transformation","volume":"8","author":"Yu","year":"2025","journal-title":"Cancer Drug Resist"},{"key":"10.1016\/j.canlet.2026.218259_bib40","article-title":"HILPDA is a prognostic biomarker and correlates with macrophage infiltration in pan-cancer","volume":"11","author":"Liu","year":"2021","journal-title":"Front. Oncol."},{"key":"10.1016\/j.canlet.2026.218259_bib41","article-title":"NR4A1 as a potential therapeutic target in colon adenocarcinoma: a computational analysis of immune infiltration and drug response","volume":"14","author":"Li","year":"2023","journal-title":"Front. Genet."},{"key":"10.1016\/j.canlet.2026.218259_bib42","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/s41586-019-0979-8","article-title":"Genome-wide analysis identifies NR4A1 as a key mediator of T cell dysfunction","volume":"567","author":"Liu","year":"2019","journal-title":"Nature"},{"key":"10.1016\/j.canlet.2026.218259_bib43","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1002\/ijc.33280","article-title":"Interleukin\u20106\u2010mediated resistance to immunotherapy is linked to impaired myeloid cell function","volume":"148","author":"Beyranvand Nejad","year":"2021","journal-title":"Int. J. Cancer"},{"key":"10.1016\/j.canlet.2026.218259_bib44","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1186\/s12935-021-02350-8","article-title":"Correlation of CCL8 expression with immune cell infiltration of skin cutaneous melanoma: potential as a prognostic indicator and therapeutic pathway","volume":"21","author":"Yang","year":"2021","journal-title":"Cancer Cell Int."},{"issue":"4","key":"10.1016\/j.canlet.2026.218259_bib45","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1007\/s43657-023-00154-6","article-title":"Modulating and imaging macrophage reprogramming for cancer immunotherapy","volume":"4","author":"Wang","year":"2024","journal-title":"Phenomics"},{"key":"10.1016\/j.canlet.2026.218259_bib46","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1038\/s41568-020-0272-z","article-title":"The cancer\u2013natural killer cell immunity cycle","volume":"20","author":"Huntington","year":"2020","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.canlet.2026.218259_bib47","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.3389\/fimmu.2019.01354","article-title":"Progressive impairment of NK cell cytotoxic degranulation is associated with TGF-\u03b21 deregulation and disease progression in pancreatic cancer","volume":"10","author":"Jun","year":"2019","journal-title":"Front. Immunol."},{"issue":"1","key":"10.1016\/j.canlet.2026.218259_bib48","doi-asserted-by":"crossref","DOI":"10.1016\/j.esmoop.2024.104088","article-title":"Anti-IL-6R Ab tocilizumab to treat paraneoplastic inflammatory syndrome of solid cancers","volume":"10","author":"Blay","year":"2025","journal-title":"ESMO Open"}],"container-title":["Cancer Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0304383526000224?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0304383526000224?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T07:51:30Z","timestamp":1773993090000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0304383526000224"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":48,"alternative-id":["S0304383526000224"],"URL":"https:\/\/doi.org\/10.1016\/j.canlet.2026.218259","relation":{},"ISSN":["0304-3835"],"issn-type":[{"value":"0304-3835","type":"print"}],"subject":[],"published":{"date-parts":[[2026,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"IL-6 drives chemoimmunotherapy resistance in NSCLC by reprogramming myeloid cells and impairing cytotoxic lymphocyte function","name":"articletitle","label":"Article Title"},{"value":"Cancer Letters","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.canlet.2026.218259","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"218259"}}