國家衛生研究院 NHRI:Item 3990099045/7728
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    题名: A novel cancer therapeutic using thrombospondin 1 in dendritic cells
    作者: Weng, TY;Huang, SS;Yen, MC;Lin, CC;Chen, YL;Lin, CM;Chen, WC;Wang, CY;Chang, JY;Lai, MD
    贡献者: National Institute of Cancer Research
    摘要: Induction of thrombospondin 1 (TSP-1) is generally assumed to suppress tumor growth through inhibiting angiogenesis; however, it is less clear how TSP-1 in dendritic cells (DCs) influences tumor progression. We investigated tumor growth and immune mechanism by downregulation of TSP-1 in dendritic cells. Administration of TSP-1 small hairpin RNA (shRNA) through the skin produced anticancer therapeutic effects. Tumor-infiltrating CD4+ and CD8+ T cells were increased after the administration of TSP-1 shRNA. The expression of interleukin-12 and interferon-gamma in the lymph nodes was enhanced by injection of TSP-1 shRNA. Lymphocytes from the mice injected with TSP-1 shRNA selectively killed the tumor cells, and the cytotoxicity of lymphocytes was abolished by depletion of CD8+ T cells. Injection of CD11c+ TSP-1-knockout (TSP-1-KO) bone marrow-derived DCs (BMDCs) delayed tumor growth in tumor-bearing mice. Similarly, antitumor activity induced by TSP-1-KO BMDCs was abrogated by depletion of CD8+ T cells. In contrast, the administration of shRNAs targeting TSP-2, another TSP family member, did not extend the survival of tumor-bearing mice. Finally, TSP-1 shRNA functioned as an immunotherapeutic adjuvant to augment the therapeutic efficacy of Neu DNA vaccination. Collectively, the downregulation of TSP-1 in DCs produces an effective antitumor response that is opposite to the protumor effects by silencing of TSP-1 within tumor cells.
    日期: 2014-02
    關聯: Molecular Therapy. 2014 Feb;22(2):292-302.
    Link to: http://dx.doi.org/10.1038/mt.2013.236
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1525-0016&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000330753900010
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84895904317
    显示于类别:[張俊彥] 期刊論文

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