{
  "abstract": "Background Despite a series of attempts during the last decades, the prognosis for esophageal squamous cell carcinoma (ESCC) remains poor. Although clinical immunotherapy trials have shown encouraging results, their benefits are limited. This study aims to identify novel targets for immunotherapy in ESCC.Experimental design ESCC cell lines and mouse models were used to identify the tumor-promoting function of pancreatic progenitor cell differentiation and proliferation factor (PPDPF) and evaluate the effect of blockade of CD24. RNA sequencing was performed to profile transcriptomic changes upon PPDPF deficiency. Fluorescence microscopy-based phagocytosis assay and flow cytometry were employed to analyze macrophage phagocytosis. Immunoblotting, glutathione S-transferase-pulldown assay and co-immunoprecipitation assay were conducted to investigate the mechanism underlying the tumor-promoting role of PPDPF in ESCC. Clinical samples were analyzed to further validate the findings from preclinical models.Results The expression of PPDPF was significantly upregulated in ESCC. Deficiency of PPDPF inhibited the development of ESCC in mice. Mechanistically, PPDPF interfered with the c-Myc-GSK3β interaction and enhanced the protein stability of c-Myc, which increased the expression of CD24 and therefore promoted immune escape from macrophage phagocytosis. Positive correlations between PPDPF, c-Myc, and CD24 were observed in clinical samples. Anti-CD24 monotherapy effectively inhibited the ESCC tumor growth in mice.Conclusions PPDPF acts as an oncoprotein in ESCC by positively regulating the c-Myc/CD24 axis. These findings provide a potential effective target for immunotherapy in ESCC.",
  "authors": [
    {
      "affiliations": [
        "Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China",
        "Zhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology, The Fifth Affiliated Hospital of Wenzhou Medical University,Department of Radiology, Lishui Central Hospital, Lishui, Zhejiang, China"
      ],
      "name": "Bing Zhu"
    },
    {
      "affiliations": [
        "Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Ning Ma"
    },
    {
      "affiliations": [
        "Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Zhi-Chao Liu"
    },
    {
      "affiliations": [
        "Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China",
        "School of Life Science and Technology, ShanghaiTech University, Shanghai, China"
      ],
      "name": "Qian-Wen Zheng"
    },
    {
      "affiliations": [
        "Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China"
      ],
      "name": "Xin Liang"
    },
    {
      "affiliations": [
        "Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China"
      ],
      "name": "Yu Chen"
    },
    {
      "affiliations": [
        "Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Yi-Kang Wang"
    },
    {
      "affiliations": [
        "Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China"
      ],
      "name": "Hui-Jun Cao"
    },
    {
      "affiliations": [
        "Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China"
      ],
      "name": "Ji Xia"
    },
    {
      "affiliations": [
        "Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China"
      ],
      "name": "Sheng Xu"
    },
    {
      "affiliations": [
        "Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China",
        "School of Life Science and Technology, ShanghaiTech University, Shanghai, China"
      ],
      "name": "Xiao-Song Qiu"
    },
    {
      "affiliations": [
        "Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China"
      ],
      "name": "Jing-Yi Huang"
    },
    {
      "affiliations": [
        "Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China"
      ],
      "name": "Kai Ding"
    },
    {
      "affiliations": [
        "Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China"
      ],
      "name": "Yan-Jun Xiang"
    },
    {
      "affiliations": [
        "Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China"
      ],
      "name": "Xi-Ran Zhang"
    },
    {
      "affiliations": [
        "Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China"
      ],
      "name": "Lin Qiu"
    },
    {
      "affiliations": [
        "Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China"
      ],
      "name": "Wei Chen"
    },
    {
      "affiliations": [
        "Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province. Affiliated Hangzhou First People's Hospital, West Lake University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Xiang Wang"
    },
    {
      "affiliations": [
        "Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China"
      ],
      "name": "Lingyun Long"
    },
    {
      "affiliations": [
        "Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China"
      ],
      "name": "Qian-Zhi Ni"
    },
    {
      "affiliations": [
        "Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Zhi-Gang Li"
    },
    {
      "affiliations": [
        "College of Biomedicine and Health, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, China",
        "Hubei Hongshan Laboratory, Wuhan, Hubei, China"
      ],
      "name": "Fan Yao"
    },
    {
      "affiliations": [
        "Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China",
        "NHC Key Laboratory of Food Safety Risk Assessment, China National Center for Food Safety Risk Assessment, Beijing, China"
      ],
      "name": "Jing-Jing Li"
    }
  ],
  "title": "PPDPF promotes the progression of esophageal squamous cell carcinoma via c-Myc/CD24 axis",
  "uid": "b985e38d-8536-5a39-a278-3de9f2d08be0"
}