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041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Chen, BaoQing
|0 0000-0001-9807-7425
|b 0
245 _ _ |a Serum 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.
260 _ _ |a London
|c 2026
|b BioMed Central
336 7 _ |a article
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336 7 _ |a ARTICLE
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520 _ _ |a Chemoradiotherapy (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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650 _ 7 |a CCL3
|2 Other
650 _ 7 |a CCL4
|2 Other
650 _ 7 |a CRT
|2 Other
650 _ 7 |a Cytokine
|2 Other
650 _ 7 |a ESCC
|2 Other
650 _ 7 |a IL-8
|2 Other
650 _ 7 |a anti-PD-1
|2 Other
650 _ 7 |a Cytokines
|2 NLM Chemicals
650 _ 7 |a Biomarkers, Tumor
|2 NLM Chemicals
650 _ 7 |a Immune Checkpoint Inhibitors
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Esophageal Squamous Cell Carcinoma: blood
|2 MeSH
650 _ 2 |a Esophageal Squamous Cell Carcinoma: mortality
|2 MeSH
650 _ 2 |a Esophageal Squamous Cell Carcinoma: therapy
|2 MeSH
650 _ 2 |a Esophageal Squamous Cell Carcinoma: drug therapy
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Chemoradiotherapy: methods
|2 MeSH
650 _ 2 |a Cytokines: blood
|2 MeSH
650 _ 2 |a Esophageal Neoplasms: blood
|2 MeSH
650 _ 2 |a Esophageal Neoplasms: mortality
|2 MeSH
650 _ 2 |a Esophageal Neoplasms: therapy
|2 MeSH
650 _ 2 |a Esophageal Neoplasms: drug therapy
|2 MeSH
650 _ 2 |a Middle Aged
|2 MeSH
650 _ 2 |a Aged
|2 MeSH
650 _ 2 |a Biomarkers, Tumor: blood
|2 MeSH
650 _ 2 |a Immune Checkpoint Inhibitors: therapeutic use
|2 MeSH
650 _ 2 |a Immune Checkpoint Inhibitors: pharmacology
|2 MeSH
650 _ 2 |a Prognosis
|2 MeSH
700 1 _ |a Chen, Junying
|0 0000-0001-7732-4319
|b 1
700 1 _ |a Wang, Sifen
|b 2
700 1 _ |a Bai, Kunhao
|b 3
700 1 _ |a Li, Zimeng
|b 4
700 1 _ |a Chen, Biqi
|0 0009-0000-9388-2820
|b 5
700 1 _ |a Wang, Ruixi
|b 6
700 1 _ |a Cheng, Xingyuan
|b 7
700 1 _ |a Gao, Yilu
|b 8
700 1 _ |a Yi, Chen
|b 9
700 1 _ |a Cen, Peiying
|b 10
700 1 _ |a Li, Shuangjiang
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700 1 _ |a Dragomir, Mihnea P
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700 1 _ |a Zhu, Yujia
|b 13
700 1 _ |a Li, Qiaoqiao
|0 0000-0002-6299-4966
|b 14
700 1 _ |a Yang, Hong
|0 0000-0002-6007-9086
|b 15
700 1 _ |a Xi, Mian
|0 0000-0002-8088-0970
|b 16
773 _ _ |a 10.1136/jitc-2025-013065
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