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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.
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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.
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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
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