TY - JOUR AU - Chen, BaoQing AU - Chen, Junying AU - Wang, Sifen AU - Bai, Kunhao AU - Li, Zimeng AU - Chen, Biqi AU - Wang, Ruixi AU - Cheng, Xingyuan AU - Gao, Yilu AU - Yi, Chen AU - Cen, Peiying AU - Li, Shuangjiang AU - Dragomir, Mihnea P AU - Zhu, Yujia AU - Li, Qiaoqiao AU - Yang, Hong AU - Xi, Mian TI - 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. JO - Journal for ImmunoTherapy of Cancer VL - 14 IS - 1 SN - 2051-1426 CY - London PB - BioMed Central M1 - DKFZ-2026-00098 SP - e013065 PY - 2026 N1 - #DKTKZFB26# AB - 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 KW - Humans KW - Male KW - Esophageal Squamous Cell Carcinoma: blood KW - Esophageal Squamous Cell Carcinoma: mortality KW - Esophageal Squamous Cell Carcinoma: therapy KW - Esophageal Squamous Cell Carcinoma: drug therapy KW - Female KW - Chemoradiotherapy: methods KW - Cytokines: blood KW - Esophageal Neoplasms: blood KW - Esophageal Neoplasms: mortality KW - Esophageal Neoplasms: therapy KW - Esophageal Neoplasms: drug therapy KW - Middle Aged KW - Aged KW - Biomarkers, Tumor: blood KW - Immune Checkpoint Inhibitors: therapeutic use KW - Immune Checkpoint Inhibitors: pharmacology KW - Prognosis KW - CCL3 (Other) KW - CCL4 (Other) KW - CRT (Other) KW - Cytokine (Other) KW - ESCC (Other) KW - IL-8 (Other) KW - anti-PD-1 (Other) KW - Cytokines (NLM Chemicals) KW - Biomarkers, Tumor (NLM Chemicals) KW - Immune Checkpoint Inhibitors (NLM Chemicals) LB - PUB:(DE-HGF)16 C6 - pmid:41526165 DO - DOI:10.1136/jitc-2025-013065 UR - https://inrepo02.dkfz.de/record/307626 ER -