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    題名: Tumor-derived interleukin-1 receptor antagonist exhibits immunosuppressive functions and promotes pancreatic cancer
    作者: 蔡淵欽
    Fan, Yu-Ching;Fong, Yu-Cin;Kuo, Chun-Tse;Li, Chia-Wei;Chen, Wei-Yu;Lin, Jian-Da;B?rtin, Florian;Linnebacher, Michael;Bui, Quoc Thang;Tsa, Kuan-Der Lee & Yuan-Chin
    貢獻者: 醫學科技學院癌症生物學與藥物研發研究所
    關鍵詞: Pancreatic adenocarcinoma;interleukin-1 receptor antagonist;Immunosuppression;Tumor microenvironment;IFN-γ;Patient-derived xenograft
    日期: 2023-10
    上傳時間: 2024-12-04 14:06:01 (UTC+8)
    摘要: Background: Pancreatic ductal adenocarcinoma (PDA) is a pernicious disease characterized by an immunosuppressive milieu that is unresponsive to current immunotherapies. Interleukin-1 receptor antagonist (IL-1Ra) is a natural anti-inflammatory cytokine; however; its contribution to cancer pathogenesis and immunosuppression remains elusive. In this research; we investigated the role and mechanism of IL-1Ra in malignant progression of PDA.

    Results: Through analyzing clinical dataset and examining the pathological tumor tissues and serum samples; we have demonstrated that IL-1Ra expression is elevated in human PDA and positively associated with malignant progression of PDA. To study the biological function of IL-1Ra in tumors; we generated a set of mouse pancreatic cancer cell lines with a knockout (KO) of the Il1rn gene; encoding IL-1Ra; and compared the tumor growth rates in immune-competent and immune-deficient mice. We found that the Il1rn KO cells exhibited greater tumor inhibition in immune-competent mice; highlighting the crucial role of a functional immune system in Il1rn KO-mediated anti-tumor response. Consistently; we found an increase in CD8+ T cells and a decrease in CD11b+Ly6G- immunosuppressive mononuclear population in the tumor microenvironment of Il1rn KO-derived tumors. To monitor the inhibitory effects of IL-1Ra on immune cells; we utilized a luciferase-based reporter CD4+ T cell line and splenocytes; which were derived from transgenic mice expressing ovalbumin-specific T cell receptors in CD8+ T cells; and mice immunized with ovalbumin. We showed that IL-1Ra suppressed T cell receptor signaling and inhibited antigen-specific interferon-γ (IFN-γ) secretion and cytolytic activity in splenocytes.

    Conclusions: Our findings illustrate the immunosuppressive properties of the natural anti-inflammatory cytokine IL-1Ra; and provide a rationale for considering IL-1Ra-targeted therapies in the treatment of PDA.
    關聯: Cell Biosci 13; 147
    描述: 【112-2 升等】臺北醫學大學教師升等專門著作
    職別：專任
    送審等級：教授
    著作送審
    附註: 代表著作名稱：《Tumor-derived interleukin-1 receptor antagonist exhibits immunosuppressive functions and promotes pancreatic cancer》
    ? 2023. Society of Chinese Bioscientists in America (SCBA).
    資料類型: article
    顯示於類別:[教師升等送審著作] 112

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