{
  "abstract": "Background Although some tumors respond to immune checkpoint blockade therapy, checkpoint inhibitors have been unsuccessful in treating uterine corpus endometrial cancer (UCEC), and the underlying molecular mechanisms remain unclear.Methods We investigated glucose flux regulation in UCEC cells with a focus on the hexosamine biosynthesis pathway (HBP). The role of O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) and its interaction with the glucocorticoid receptor (GR) were examined using in vitro and in vivo models. A competitive peptide was designed to disrupt the interaction between OGT and GR.Results We found that UCEC cells direct glucose flux to the HBP. OGT, a critical enzyme for protein O-GlcNAcylation, increased programmed death ligand-1 (PD-L1) expression while decreasing major histocompatibility complex class I (MHC-I) expression, thereby promoting immune evasion and resistance to immunotherapy. Mechanistically, OGT interacted with GR, leading to O-GlcNAcylation of GR at serine 132, which required prior phosphorylation of GR. Disruptions of the OGT–GR interaction with the competitive peptide reduced GR O-GlcNAcylation, decreased PD-L1 expression, and increased MHC-I expression. This, in turn, activated CD8+ T cell-mediated immunity against tumor cells in vitro and in vivo.Conclusions Our findings reveal cross-talk between the HBP, steroid hormone pathway, and tumor immune evasion, and suggest potential strategies for sensitizing UCEC to immunotherapy.",
  "authors": [
    {
      "affiliations": [
        "Longnan Hospital, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China",
        "Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, China"
      ],
      "name": "Jingjing Wang"
    },
    {
      "affiliations": [
        "Longnan Hospital, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China"
      ],
      "name": "Yang Xie"
    },
    {
      "affiliations": [
        "Longnan Hospital, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China"
      ],
      "name": "Li Liu"
    },
    {
      "affiliations": [
        "State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Taikang Center for Life and Medical Sciences, Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, China"
      ],
      "name": "Shuo Rong"
    },
    {
      "affiliations": [
        "Department of Cardiology, Zhongnan Hospital of Wuhan University, Institute of Myocardial Injury and Repair, Wuhan University, Wuhan, China"
      ],
      "name": "Huanhuan Cai"
    },
    {
      "affiliations": [
        "State Key Laboratory Breeding Base of Basic Science of Stomatology (HubeiMOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China"
      ],
      "name": "Hao Zeng"
    },
    {
      "affiliations": [
        "State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Taikang Center for Life and Medical Sciences, Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, China"
      ],
      "name": "Li Zhou"
    },
    {
      "affiliations": [
        "Department of Cardiology, Zhongnan Hospital of Wuhan University, Institute of Myocardial Injury and Repair, Wuhan University, Wuhan, China"
      ],
      "name": "Keqiong Deng"
    },
    {
      "affiliations": [
        "Longnan Hospital, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China"
      ],
      "name": "Mengqiao Dai"
    },
    {
      "affiliations": [
        "Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, China"
      ],
      "name": "Chao Xu"
    },
    {
      "affiliations": [
        "State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Taikang Center for Life and Medical Sciences, Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, China"
      ],
      "name": "Ying Zhu"
    },
    {
      "affiliations": [
        "Department of Cardiology, Zhongnan Hospital of Wuhan University, Institute of Myocardial Injury and Repair, Wuhan University, Wuhan, China"
      ],
      "name": "Zhibing Lu"
    },
    {
      "affiliations": [
        "The Research Centre of Anesthesiology and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China"
      ],
      "name": "Xuemin Song"
    },
    {
      "affiliations": [
        "Longnan Hospital, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China"
      ],
      "name": "Xiangtai Zeng"
    },
    {
      "affiliations": [
        "Longnan Hospital, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China",
        "State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Taikang Center for Life and Medical Sciences, Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, China",
        "Department of Cardiology, Zhongnan Hospital of Wuhan University, Institute of Myocardial Injury and Repair, Wuhan University, Wuhan, China"
      ],
      "name": "Shi Liu"
    }
  ],
  "title": "O-GlcNAc transferase promotes immune evasion and immunotherapy resistance in uterine corpus endometrial cancer by targeting the glucocorticoid receptor",
  "uid": "ca428a77-5873-55db-ad92-072be788fdd8"
}