{
  "abstract": "Background\n\nc-MET is implicated in ESCC progression, but whether c-MET inhibition reshapes immune checkpoint expression and the tumor immune microenvironment remains unclear.Methods\n\nESCC cell lines were treated with Tepotinib, and c-MET and PD-L1 expression were examined by Western blotting and immunofluorescence. MET knockdown was performed in TE-1 and KYSE150 cells. AKR syngeneic subcutaneous tumor models were used to assess PD-L1 and PD-1 expression, immune cell composition, transcriptomic and proteomic changes, NF-κB/p65 signaling, and the efficacy of Tepotinib combined with an anti-PD-1 antibody.Results\n\nTepotinib decreased c-MET expression and increased PD-L1 expression in ESCC cells. MET knockdown produced a similar increase in PD-L1. In vivo, Tepotinib increased PD-L1 and PD-1 expression in tumor tissues and increased PD-L1 expression in the CD45⁻ non-immune compartment, together with decreased CD8⁺ T cells and cDC1 cells, increased Treg cells, and increased CD206 expression in tumor-associated macrophages. Dual immunofluorescence and quantitative analysis further showed an increased proportion of CD8⁺PD-1⁺ cells among total CD8⁺ cells in Tepotinib-treated tumors. Transcriptomic and proteomic analyses indicated enrichment of inflammatory and immune-related pathways, including NF-κB, TNF, JAK-STAT, and immune checkpoint-related signaling. Tepotinib increased p65 phosphorylation, whereas NF-κB inhibition reduced p-p65 and PD-L1 expression. Tepotinib combined with anti-PD-1 antibody reduced tumor burden and delayed humane endpoint events compared with monotherapy.Conclusions\n\nc-MET inhibition is accompanied by adaptive PD-L1 upregulation and immunosuppression-related changes in the tumor microenvironment in ESCC. NF-κB/p65 signaling may participate in this response. The enhanced antitumor activity observed with Tepotinib plus anti-PD-1 therapy supports further investigation of this combination strategy.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Chuan Song",
      "orcid": "0009-0001-8414-5527"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhe Xia"
    },
    {
      "affs": [
        0
      ],
      "name": "Hu Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xinyu Wang",
      "orcid": "0000-0002-3279-2212"
    },
    {
      "affs": [
        0
      ],
      "name": "Jing Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Binbin Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Chen Feng",
      "orcid": "0000-0002-0370-8894"
    },
    {
      "affs": [
        0
      ],
      "name": "Bo Xie"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1sew5ybpqn0rs.bib",
  "cited_by": 0,
  "doi": "10.1002/cam4.72428",
  "fulltext_url": "https://europepmc.org/articles/PMC13724753",
  "id": "1sew5ybpqn0rs",
  "issns": [
    "2045-7634"
  ],
  "landing_url": "https://europepmc.org/article/MED/42968226",
  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
    ]
  ],
  "openalex": "W7225087431",
  "pdf_url": "https://europepmc.org/articles/PMC13724753?pdf=render",
  "pmcid": "PMC13724753",
  "pmid": "42968226",
  "published": "2026-11-01",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/1sew5ybpqn0rs.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T15:20:53Z",
      "native_id": "MED:42968226",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42968226"
    },
    {
      "first_seen": "2026-11-04T12:23:16Z",
      "native_id": "PMC13724753",
      "source": "pmc",
      "url": "https://doi.org/10.1002/cam4.72428"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers",
      "subfield": "oncology"
    }
  ],
  "title": "c-MET Inhibition Is Accompanied by PD-L1 Upregulation and Immunosuppression-Related Tumor Microenvironment Changes in Esophageal Squamous Cell Carcinoma, With Enhanced Antitumor Activity in Combination With Anti-PD-1 Therapy.",
  "title_text": "c-MET Inhibition Is Accompanied by PD-L1 Upregulation and Immunosuppression-Related Tumor Microenvironment Changes in Esophageal Squamous Cell Carcinoma, With Enhanced Antitumor Activity in Combination With Anti-PD-1 Therapy.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:21:09Z",
  "url": "https://research.draconitic.com/paper/1sew5ybpqn0rs",
  "venue": "Cancer medicine",
  "versions": []
}