國家衛生研究院 NHRI:Item 3990099045/11332
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    题名: Locally targeting the IL-17/ IL-17RA axis reduced tumor growth in a murine B16F10 melanoma model
    作者: Chen, YS;Huang, TH;Liu, CL;Chen, HS;Lee, MH;Chen, HW;Shen, CR
    贡献者: National Institute of Infectious Diseases and Vaccinology
    摘要: Interleukin 17 (IL-17) and its producing cells within the tumor microenvironment appear to promote tumor development and associate with survival of cancer patients. Here we investigated the role of the IL-17/IL- 17 receptor A (IL-17RA) axis in regulating melanoma progression and evaluated the therapeutic potential of blocking the IL-17/IL-17RA pathway. First, recombinant mouse IL-17 (gammamIL-17) treatment significantly increased cell proliferation of mouse B16F10 and human A375 and A2058. Silencing IL-17RA by small hairpin RNA (shRNA) in B16F10 cells reduced the gammamIL-17 elicited cell proliferation, migration and invasion, and significantly reduced VEGF and MMP production. Remarkably, knockdown of IL-17RA led to a significantly decreased capability of B16F10 cells to form tumors in vivo, similar to that in IL-17- deficient mice. Finally, local application of adenovirus delivering a shRNA against IL-17RA not only significantly suppressed tumor development, but also enhanced anti-tumor immunity by increasing the IFNgamma-expressing T cells and not Treg cells. Our results highlight the critical role of the IL-17/IL- 17RA pathway in tumor progression, and imply that targeting IL-17RA represents a promising therapeutic strategy.
    日期: 2019-03
    關聯: Human Gene Therapy. 2019 Mar;3(3):273-285.
    Link to: http://dx.doi.org/10.1089/hum.2018.104
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1043-0342&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000446273400001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=https://www.scopus.com/inward/record.uri?eid=2-s2.0-85062595728&partnerID=40
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