{
  "abstract": "Purpose 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.Experimental Design 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.Results 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.Conclusions 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.",
  "authors": [
    {
      "affiliations": [
        "Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Reasearch Center for Cancer, Sun Yat-sen University Cancer Center, Guangdong Esophageal Cancer Institute, Guangzhou, Guangdong, China",
        "United Laboratory of Frontier Radiotherapy Technology of Sun Yat-sen University & Chinese Academy of Sciences Ion Medical Technology Co., Ltd, Guangzhou, China"
      ],
      "name": "BaoQing Chen"
    },
    {
      "affiliations": [
        "Department of Thoracic Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangdong Esophageal Cancer Institute, Guangzhou, Guangdong, China"
      ],
      "name": "Junying Chen"
    },
    {
      "affiliations": [
        "Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Reasearch Center for Cancer, Sun Yat-sen University Cancer Center, Guangdong Esophageal Cancer Institute, Guangzhou, Guangdong, China"
      ],
      "name": "Sifen Wang"
    },
    {
      "affiliations": [
        "Department of Endoscopy, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangdong Esophageal Cancer Institute, Guangzhou, Guangdong, China"
      ],
      "name": "Kunhao Bai"
    },
    {
      "affiliations": [
        "Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Reasearch Center for Cancer, Sun Yat-sen University Cancer Center, Guangdong Esophageal Cancer Institute, Guangzhou, Guangdong, China"
      ],
      "name": "Zimeng Li"
    },
    {
      "affiliations": [
        "Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Reasearch Center for Cancer, Sun Yat-sen University Cancer Center, Guangdong Esophageal Cancer Institute, Guangzhou, Guangdong, China"
      ],
      "name": "Biqi Chen"
    },
    {
      "affiliations": [
        "Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Reasearch Center for Cancer, Sun Yat-sen University Cancer Center, Guangdong Esophageal Cancer Institute, Guangzhou, Guangdong, China"
      ],
      "name": "Ruixi Wang"
    },
    {
      "affiliations": [
        "Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Reasearch Center for Cancer, Sun Yat-sen University Cancer Center, Guangdong Esophageal Cancer Institute, Guangzhou, Guangdong, China"
      ],
      "name": "Xingyuan Cheng"
    },
    {
      "affiliations": [
        "Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Reasearch Center for Cancer, Sun Yat-sen University Cancer Center, Guangdong Esophageal Cancer Institute, Guangzhou, Guangdong, China"
      ],
      "name": "Yilu Gao"
    },
    {
      "affiliations": [
        "Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Reasearch Center for Cancer, Sun Yat-sen University Cancer Center, Guangdong Esophageal Cancer Institute, Guangzhou, Guangdong, China"
      ],
      "name": "Chen Yi"
    },
    {
      "affiliations": [
        "Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Reasearch Center for Cancer, Sun Yat-sen University Cancer Center, Guangdong Esophageal Cancer Institute, Guangzhou, Guangdong, China"
      ],
      "name": "Peiying Cen"
    },
    {
      "affiliations": [
        "Department of Endoscopy, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangdong Esophageal Cancer Institute, Guangzhou, Guangdong, China"
      ],
      "name": "Shuangjiang Li"
    },
    {
      "affiliations": [
        "Institute of Pathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany",
        "Berlin Institute of Health, Berlin, Germany",
        "German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany"
      ],
      "name": "Mihnea P Dragomir"
    },
    {
      "affiliations": [
        "Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Reasearch Center for Cancer, Sun Yat-sen University Cancer Center, Guangdong Esophageal Cancer Institute, Guangzhou, Guangdong, China"
      ],
      "name": "Yujia Zhu"
    },
    {
      "affiliations": [
        "Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Reasearch Center for Cancer, Sun Yat-sen University Cancer Center, Guangdong Esophageal Cancer Institute, Guangzhou, Guangdong, China"
      ],
      "name": "Qiaoqiao Li"
    },
    {
      "affiliations": [
        "Department of Thoracic Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangdong Esophageal Cancer Institute, Guangzhou, Guangdong, China"
      ],
      "name": "Hong Yang"
    },
    {
      "affiliations": [
        "Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Reasearch Center for Cancer, Sun Yat-sen University Cancer Center, Guangdong Esophageal Cancer Institute, Guangzhou, Guangdong, China",
        "United Laboratory of Frontier Radiotherapy Technology of Sun Yat-sen University & Chinese Academy of Sciences Ion Medical Technology Co., Ltd, Guangzhou, China"
      ],
      "name": "Mian Xi"
    }
  ],
  "title": "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",
  "uid": "1e5d8ba0-4a97-5d37-8a00-1d001ee55b3a"
}