{
  "abstract": "Background Neoadjuvant chemoimmunotherapy (NACI) has shown promising results in treating esophageal squamous cell carcinoma (ESCC), yet the mechanisms driving its efficacy remain poorly defined, limiting further optimization of this regimen.Methods To investigate the dynamics of the tumor microenvironment (TME), we integrated single-cell RNA sequencing, immunorepertoire profiling, and spatial transcriptomics across 18 samples from nine patients with ESCC undergoing NACI. Computational workflows encompassed integrated clustering, gene set enrichment, T cell receptor repertoire characterization, copy number variation estimation, and cell–cell communication inference. Spatial mapping was performed using cytoSPACE. Key findings were validated via orthogonal spatial transcriptomics, multiplex immunohistochemistry, and in vivo preclinical models.Results We identified distinct post-treatment accumulation of ACKR1+ endothelial cells (ECs) and CFD+ cancer-associated fibroblasts (CAFs) at tumor boundaries, potentially correlating with enhanced CD8+ T cell infiltration and improved clinical outcomes. Conversely, treatment-resistant tumors exhibited VEGFA-driven upregulation in malignant cells, promoting RGCC+ ECs with elevated VEGFR2 expression. These RGCC+ ECs synergized with MMP11+ CAFs to form a collagen-rich tumor niche that fostered malignancy and immunosuppression. Importantly, targeting VEGFR2 not only improved therapeutic response but also reversed immune suppression.Conclusions This study reveals that stromal cells such as CAFs and ECs within the TME collaboratively determine NACI efficacy in ESCC. These findings could offer novel theoretical insights and actionable strategies for enhancing treatment efficacy in ESCC.",
  "authors": [
    {
      "affiliations": [
        "Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China",
        "State Key Laboratory of Respiratory Disease, Guangzhou, Guangdong, China"
      ],
      "name": "Zhongjian Yu"
    },
    {
      "affiliations": [
        "School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China",
        "Guangzhou National Laboratory, Guangzhou, Guangdong, China"
      ],
      "name": "Wenjia Li"
    },
    {
      "affiliations": [
        "Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China",
        "State Key Laboratory of Respiratory Disease, Guangzhou, Guangdong, China"
      ],
      "name": "Shiting Xu"
    },
    {
      "affiliations": [
        "Guangzhou National Laboratory, Guangzhou, Guangdong, China",
        "Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong, China"
      ],
      "name": "Meng Xu"
    },
    {
      "affiliations": [
        "Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Qi Lin"
    },
    {
      "affiliations": [
        "Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China",
        "State Key Laboratory of Respiratory Disease, Guangzhou, Guangdong, China"
      ],
      "name": "Lu Liu"
    },
    {
      "affiliations": [
        "Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Jiangyu Zhang"
    },
    {
      "affiliations": [
        "Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Xi Zhong"
    },
    {
      "affiliations": [
        "Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Chuan Jin"
    },
    {
      "affiliations": [
        "Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Liu Zuo"
    },
    {
      "affiliations": [
        "Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China",
        "State Key Laboratory of Respiratory Disease, Guangzhou, Guangdong, China"
      ],
      "name": "Rui Cai"
    },
    {
      "affiliations": [
        "Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China",
        "State Key Laboratory of Respiratory Disease, Guangzhou, Guangdong, China"
      ],
      "name": "Meng Wang"
    },
    {
      "affiliations": [
        "Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China",
        "State Key Laboratory of Respiratory Disease, Guangzhou, Guangdong, China"
      ],
      "name": "Hongxin Huang"
    },
    {
      "affiliations": [
        "Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Xiongjie Zhu"
    },
    {
      "affiliations": [
        "SA-Center for Interdisciplinary Research in Basic Sciences, International Islamic University, Islamabad, Pakistan"
      ],
      "name": "Muhammad Riaz"
    },
    {
      "affiliations": [
        "Guangzhou National Laboratory, Guangzhou, Guangdong, China",
        "State Key Laboratory of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Shengbao Suo"
    },
    {
      "affiliations": [
        "Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Ming Zhou"
    },
    {
      "affiliations": [
        "Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China",
        "State Key Laboratory of Respiratory Disease, Guangzhou, Guangdong, China"
      ],
      "name": "Yanfang Zheng"
    }
  ],
  "title": "Targeting VEGF signaling and stromal remodeling enhances chemoimmunotherapy efficacy in esophageal cancer",
  "uid": "71899b77-eca9-5f1f-bfba-8ccf7649c3ff"
}