{
  "abstract": "Introduction Understanding the negative regulatory mechanisms of immune cell functions is essential for developing effective tumor immunotherapy strategies. Macrophages play a crucial role in antitumor immunity; however, the mechanisms that negatively regulate their antitumor functions remain incompletely understood. TIPE2 is known to be a critical regulator of various immune cells, but its role as a negative regulator of macrophage antitumor functions has not yet been established.Objectives This study aims to investigate whether TIPE2 negatively regulates the antitumor functions of macrophages and to elucidate the mechanisms involved.Methods We used a mouse model of hepatic tumor metastasis and a subcutaneous tumor model to evaluate the impact of TIPE2 on macrophage antitumor functions. In vitro experiments, including fluorescence microscopy and flow cytometry, were conducted to assess whether the TIPE2 deficiency enhances the phagocytic activity of macrophages against tumor cells. Additionally, we employed co-immunoprecipitation assays along with spleen tyrosine kinase (SYK) and Ras-related C3 botulinum toxin substrate 1 (RAC1) signaling blockade assays to investigate the molecular mechanisms through which TIPE2 exerts its negative regulatory effects.Results Our findings indicate that TIPE2 gene loss in myeloid cells inhibits hepatic tumor metastasis, which is dependent on macrophages in the liver. Furthermore, macrophages lacking TIPE2 demonstrated enhanced tumor growth inhibition in subcutaneous tumor models. In vitro, these macrophages exhibited increased phagocytic activity against tumor cells. Mechanistically, TIPE2 negatively regulates the activation of SYK and RAC1, thereby modulating the phagocytic capabilities of macrophages.Conclusion TIPE2 represents a negative regulatory mechanism for macrophage phagocytosis against tumor cells. In the future, TIPE2 may serve as a promising target to enhance the efficacy of tumor immunotherapy strategies based on macrophages.",
  "authors": [
    {
      "affiliations": [
        "Department of Immunology and Shandong Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China"
      ],
      "name": "Zelong Ma"
    },
    {
      "affiliations": [
        "Department of Immunology and Shandong Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China"
      ],
      "name": "Yingyue Wang"
    },
    {
      "affiliations": [
        "Department of Immunology and Shandong Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China"
      ],
      "name": "Yanlei Dong"
    },
    {
      "affiliations": [
        "Department of Immunology and Shandong Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China"
      ],
      "name": "Hong Yuan"
    },
    {
      "affiliations": [
        "Department of Immunology and Shandong Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China"
      ],
      "name": "Ruoxuan Yang"
    },
    {
      "affiliations": [
        "Laboratory of Cellular and Molecular Medicine, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China"
      ],
      "name": "Ying Xiao"
    },
    {
      "affiliations": [
        "Department of Immunology and Shandong Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China",
        "Laboratory of Cellular and Molecular Medicine, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China"
      ],
      "name": "Chun Guo"
    },
    {
      "affiliations": [
        "Laboratory of Cellular and Molecular Medicine, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China"
      ],
      "name": "Ruirui Wang"
    },
    {
      "affiliations": [
        "Department of Immunology and Shandong Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China"
      ],
      "name": "Jianing Wang"
    },
    {
      "affiliations": [
        "Department of Immunology and Shandong Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China"
      ],
      "name": "Xiaoyan Wang"
    },
    {
      "affiliations": [
        "Department of Immunology and Shandong Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China"
      ],
      "name": "Faliang Zhu"
    },
    {
      "affiliations": [
        "Department of Immunology and Shandong Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China"
      ],
      "name": "Lining Zhang"
    },
    {
      "affiliations": [
        "Department of Hepatology, Qilu Hospital of Shandong University, Jinan, Shandong, China"
      ],
      "name": "Yuchen Fan"
    },
    {
      "affiliations": [
        "Department of Immunology and Shandong Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China"
      ],
      "name": "Yongyu Shi"
    }
  ],
  "title": "TIPE2 deficiency enhances macrophage phagocytosis of tumor cells",
  "uid": "10c4d27f-c464-5dfe-8e8c-1357d0abf43d"
}