{
  "abstract": "Background Beyond supporting cancer cell proliferation, tumor growth relies on the ability of cancer cells to evade immune surveillance. Identifying novel molecules that promote tumor immune escape may help develop more effective immunotherapeutic strategies. The histone acetyltransferase E1A-binding protein p300 (EP300) is a key epigenetic regulator that modulates gene transcription through chromatin remodeling and acetylation of histones and transcription factors. However, its role in regulating immune evasion remains incompletely understood. This study investigates the impact of EP300 on tumor immune escape and suggests its potential as an immunotherapeutic target.Methods We analyzed tissue microarrays from patients with lung adenocarcinoma using immunohistochemistry to compare EP300 expression between cancerous tissues and benign tissues. Ep300-knockout cancer cells were generated using CRISPR-Cas9. Animal models were employed to assess the effect of Ep300 depletion on tumor progression and intratumoral CD8+ T cell infiltration. RNA sequencing, chromatin immunoprecipitation sequencing, flow cytometry, and western blot were used to explore the mechanism by which EP300 regulates antigen-presenting gene expression.Results EP300 was significantly upregulated in cancerous tissues compared with benign tissues. Genetic ablation of Ep300 in cancer cells markedly suppressed tumor growth in vivo and enhanced CD8+ T-cell infiltration. Mechanistically, EP300 upregulates suppressor of cytokine signaling 1 (SOCS1) expression, thereby inhibiting signal transducer and activator of transcription 1 phosphorylation. This leads to downregulation of antigen-presenting genes, enabling cancer cells to evade immune surveillance by CD8+ T cells.Conclusions EP300 facilitates tumor immune evasion by suppressing antigen-presenting gene expression via SOCS1 upregulation. Our findings reveal a novel role for EP300 in mediating immune escape and propose a potential therapeutic strategy to enhance antitumor immunity.",
  "authors": [
    {
      "affiliations": [
        "National Key Laboratory of Immunity and Inflammation, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou, Jiangsu, China"
      ],
      "name": "Yanqiong Zeng"
    },
    {
      "affiliations": [
        "National Key Laboratory of Immunity and Inflammation, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou, Jiangsu, China",
        "Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China"
      ],
      "name": "Ying Zhou"
    },
    {
      "affiliations": [
        "National Key Laboratory of Immunity and Inflammation, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou, Jiangsu, China"
      ],
      "name": "Jiayin Ruan"
    },
    {
      "affiliations": [
        "Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, China"
      ],
      "name": "Wancheng Liu"
    },
    {
      "affiliations": [
        "National Key Laboratory of Immunity and Inflammation, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou, Jiangsu, China"
      ],
      "name": "Huimin Fan"
    },
    {
      "affiliations": [
        "National Key Laboratory of Immunity and Inflammation, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou, Jiangsu, China",
        "Nanchang University Jiangxi Medical College, Nanchang, Jiangxi, China"
      ],
      "name": "Na Liu"
    },
    {
      "affiliations": [
        "National Key Laboratory of Immunity and Inflammation, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou, Jiangsu, China"
      ],
      "name": "Lili Li"
    },
    {
      "affiliations": [
        "National Key Laboratory of Immunity and Inflammation, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou, Jiangsu, China"
      ],
      "name": "Jiayuan Ma"
    },
    {
      "affiliations": [
        "The Affiliated Tumor Hospital of Nantong University, Nantong Tumor Hospital, Nantong, Jiangsu, China"
      ],
      "name": "Xiaoxia Jin"
    },
    {
      "affiliations": [
        "Department of Rheumatology and Clinical Immunology, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, China"
      ],
      "name": "Lihua Duan"
    },
    {
      "affiliations": [
        "Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China"
      ],
      "name": "Youguo Chen"
    },
    {
      "affiliations": [
        "National Key Laboratory of Immunity and Inflammation, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou, Jiangsu, China"
      ],
      "name": "Genhong Cheng"
    },
    {
      "affiliations": [
        "National Key Laboratory of Immunity and Inflammation, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou, Jiangsu, China"
      ],
      "name": "Heng Yang"
    }
  ],
  "title": "EP300 compromises antitumor immunity by increasing SOCS1 expression",
  "uid": "d542c4c1-f155-5e0e-8483-cf5fa16604d3"
}