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@ARTICLE{Chen:307626,
      author       = {B. Chen and J. Chen and S. Wang and K. Bai and Z. Li and B.
                      Chen and R. Wang and X. Cheng and Y. Gao and C. Yi and P.
                      Cen and S. Li and M. P. Dragomir$^*$ and Y. Zhu and Q. Li
                      and H. Yang and M. Xi},
      title        = {{S}erum 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.},
      journal      = {Journal for ImmunoTherapy of Cancer},
      volume       = {14},
      number       = {1},
      issn         = {2051-1426},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DKFZ-2026-00098},
      pages        = {e013065},
      year         = {2026},
      note         = {#DKTKZFB26#},
      abstract     = {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.},
      keywords     = {Humans / Male / Esophageal Squamous Cell Carcinoma: blood /
                      Esophageal Squamous Cell Carcinoma: mortality / Esophageal
                      Squamous Cell Carcinoma: therapy / Esophageal Squamous Cell
                      Carcinoma: drug therapy / Female / Chemoradiotherapy:
                      methods / Cytokines: blood / Esophageal Neoplasms: blood /
                      Esophageal Neoplasms: mortality / Esophageal Neoplasms:
                      therapy / Esophageal Neoplasms: drug therapy / Middle Aged /
                      Aged / Biomarkers, Tumor: blood / Immune Checkpoint
                      Inhibitors: therapeutic use / Immune Checkpoint Inhibitors:
                      pharmacology / Prognosis / CCL3 (Other) / CCL4 (Other) / CRT
                      (Other) / Cytokine (Other) / ESCC (Other) / IL-8 (Other) /
                      anti-PD-1 (Other) / Cytokines (NLM Chemicals) / Biomarkers,
                      Tumor (NLM Chemicals) / Immune Checkpoint Inhibitors (NLM
                      Chemicals)},
      cin          = {BE01},
      ddc          = {610},
      cid          = {I:(DE-He78)BE01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41526165},
      doi          = {10.1136/jitc-2025-013065},
      url          = {https://inrepo02.dkfz.de/record/307626},
}