000307626 001__ 307626 000307626 005__ 20260114120432.0 000307626 0247_ $$2doi$$a10.1136/jitc-2025-013065 000307626 0247_ $$2pmid$$apmid:41526165 000307626 037__ $$aDKFZ-2026-00098 000307626 041__ $$aEnglish 000307626 082__ $$a610 000307626 1001_ $$00000-0001-9807-7425$$aChen, BaoQing$$b0 000307626 245__ $$aSerum cytokines predict response and survival in esophageal squamous cell carcinoma receiving chemoradiotherapy combined with anti-PD-1 antibody: analyses of two phase II clinical trials. 000307626 260__ $$aLondon$$bBioMed Central$$c2026 000307626 3367_ $$2DRIVER$$aarticle 000307626 3367_ $$2DataCite$$aOutput Types/Journal article 000307626 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1768316515_488979 000307626 3367_ $$2BibTeX$$aARTICLE 000307626 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000307626 3367_ $$00$$2EndNote$$aJournal Article 000307626 500__ $$a#DKTKZFB26# 000307626 520__ $$aChemoradiotherapy (CRT) combined with anti-PD-1 for locally advanced esophageal squamous cell carcinoma (ESCC) has shown promising efficacy but lack the predictive biomarkers to identify patients who could benefit from this therapy. The predictive value of serum cytokines in ESCC patients remains unclear. We aimed to identify cytokine-based biomarkers for treatment response and survival in this setting.Exploratory analyses were conducted on 81 ESCC patients from two phase II trials treated with CRT plus toripalimab, with validation in an independent prospective cohort (n=61). Nineteen serum cytokines were assessed at baseline, during, and post-CRT plus anti-PD-1 antibody. A cytokine-based risk score model (CYTOscore) was constructed. Multi-omics profiling including RNA-seq, WES, and spatial transcriptomics were performed to explore potential differences in tumor microenvironments.Cox analyses identified Interleukin-8 (IL-8), C-C motif chemokine ligand 3 (CCL3), and C-C motif chemokine ligand 4 (CCL4) as potential biomarkers and were used to constructed the CYTOscore. Patients stratified by baseline CYTOscore showed significantly longer OS (HR, 0.31; 95%CI, 0.16-0.62; p= 0.00045) and PFS (HR, 0.33; 95%CI, 0.17-0.62; p= 0.00036) in the low-risk group, which also had higher complete response (CR) rates (66% vs 35%, p=0.014). These finding were next validated in the external cohort, with the low-risk group demonstrating higher CR rates (66% vs 27%, p=0.039) and longer OS (HR 0.30, 95% CI 0.09-0.99, p=0.045). A nomogram incorporating baseline CYTOscore and clinical characteristics showed promising predictive accuracy in 1-, 2-, and 3-year OS (AUC=0.77, 0.78, and 0.76). Multi-omics analysis revealed enriched interferon-γ/α signaling in B cells within low-risk patients.The CYTOscore based on IL-8, CCL3, and CCL4 effectively predicts treatment response and survival in ESCC patients receiving CRT plus anti-PD-1 antibody. 000307626 536__ $$0G:(DE-HGF)POF4-899$$a899 - ohne Topic (POF4-899)$$cPOF4-899$$fPOF IV$$x0 000307626 588__ $$aDataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de 000307626 650_7 $$2Other$$aCCL3 000307626 650_7 $$2Other$$aCCL4 000307626 650_7 $$2Other$$aCRT 000307626 650_7 $$2Other$$aCytokine 000307626 650_7 $$2Other$$aESCC 000307626 650_7 $$2Other$$aIL-8 000307626 650_7 $$2Other$$aanti-PD-1 000307626 650_7 $$2NLM Chemicals$$aCytokines 000307626 650_7 $$2NLM Chemicals$$aBiomarkers, Tumor 000307626 650_7 $$2NLM Chemicals$$aImmune Checkpoint Inhibitors 000307626 650_2 $$2MeSH$$aHumans 000307626 650_2 $$2MeSH$$aMale 000307626 650_2 $$2MeSH$$aEsophageal Squamous Cell Carcinoma: blood 000307626 650_2 $$2MeSH$$aEsophageal Squamous Cell Carcinoma: mortality 000307626 650_2 $$2MeSH$$aEsophageal Squamous Cell Carcinoma: therapy 000307626 650_2 $$2MeSH$$aEsophageal Squamous Cell Carcinoma: drug therapy 000307626 650_2 $$2MeSH$$aFemale 000307626 650_2 $$2MeSH$$aChemoradiotherapy: methods 000307626 650_2 $$2MeSH$$aCytokines: blood 000307626 650_2 $$2MeSH$$aEsophageal Neoplasms: blood 000307626 650_2 $$2MeSH$$aEsophageal Neoplasms: mortality 000307626 650_2 $$2MeSH$$aEsophageal Neoplasms: therapy 000307626 650_2 $$2MeSH$$aEsophageal Neoplasms: drug therapy 000307626 650_2 $$2MeSH$$aMiddle Aged 000307626 650_2 $$2MeSH$$aAged 000307626 650_2 $$2MeSH$$aBiomarkers, Tumor: blood 000307626 650_2 $$2MeSH$$aImmune Checkpoint Inhibitors: therapeutic use 000307626 650_2 $$2MeSH$$aImmune Checkpoint Inhibitors: pharmacology 000307626 650_2 $$2MeSH$$aPrognosis 000307626 7001_ $$00000-0001-7732-4319$$aChen, Junying$$b1 000307626 7001_ $$aWang, Sifen$$b2 000307626 7001_ $$aBai, Kunhao$$b3 000307626 7001_ $$aLi, Zimeng$$b4 000307626 7001_ $$00009-0000-9388-2820$$aChen, Biqi$$b5 000307626 7001_ $$aWang, Ruixi$$b6 000307626 7001_ $$aCheng, Xingyuan$$b7 000307626 7001_ $$aGao, Yilu$$b8 000307626 7001_ $$aYi, Chen$$b9 000307626 7001_ $$aCen, Peiying$$b10 000307626 7001_ $$aLi, Shuangjiang$$b11 000307626 7001_ $$0P:(DE-He78)396821e874b632341e4bcabd27bcad3f$$aDragomir, Mihnea P$$b12$$udkfz 000307626 7001_ $$aZhu, Yujia$$b13 000307626 7001_ $$00000-0002-6299-4966$$aLi, Qiaoqiao$$b14 000307626 7001_ $$00000-0002-6007-9086$$aYang, Hong$$b15 000307626 7001_ $$00000-0002-8088-0970$$aXi, Mian$$b16 000307626 773__ $$0PERI:(DE-600)2719863-7$$a10.1136/jitc-2025-013065$$gVol. 14, no. 1, p. e013065 -$$n1$$pe013065$$tJournal for ImmunoTherapy of Cancer$$v14$$x2051-1426$$y2026 000307626 909CO $$ooai:inrepo02.dkfz.de:307626$$pVDB 000307626 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)396821e874b632341e4bcabd27bcad3f$$aDeutsches Krebsforschungszentrum$$b12$$kDKFZ 000307626 9131_ $$0G:(DE-HGF)POF4-899$$1G:(DE-HGF)POF4-890$$2G:(DE-HGF)POF4-800$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bProgrammungebundene Forschung$$lohne Programm$$vohne Topic$$x0 000307626 9141_ $$y2026 000307626 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bJ IMMUNOTHER CANCER : 2022$$d2024-12-11 000307626 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2024-12-11 000307626 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2024-12-11 000307626 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2024-01-24T13:16:43Z 000307626 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2024-01-24T13:16:43Z 000307626 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bDOAJ : Anonymous peer review$$d2024-01-24T13:16:43Z 000307626 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2024-12-11 000307626 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2024-12-11 000307626 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2024-12-11 000307626 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2024-12-11 000307626 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2024-12-11 000307626 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2024-12-11 000307626 915__ $$0StatID:(DE-HGF)9910$$2StatID$$aIF >= 10$$bJ IMMUNOTHER CANCER : 2022$$d2024-12-11 000307626 915__ $$0StatID:(DE-HGF)0561$$2StatID$$aArticle Processing Charges$$d2024-12-11 000307626 915__ $$0StatID:(DE-HGF)0700$$2StatID$$aFees$$d2024-12-11 000307626 9201_ $$0I:(DE-He78)BE01-20160331$$kBE01$$lDKTK Koordinierungsstelle Berlin$$x0 000307626 980__ $$ajournal 000307626 980__ $$aVDB 000307626 980__ $$aI:(DE-He78)BE01-20160331 000307626 980__ $$aUNRESTRICTED