کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2042259 | 1073190 | 2012 | 13 صفحه PDF | دانلود رایگان |
SummaryAn increased understanding of antitumor immunity is necessary for improving cell-based immunotherapies against human cancers. Here, we investigated the roles of two immune system-expressed microRNAs (miRNAs), miR-155 and miR-146a, in the regulation of antitumor immune responses. Our results indicate that miR-155 promotes and miR-146a inhibits interferon γ (IFNγ) responses by T cells and reduces solid tumor growth in vivo. Using a double-knockout (DKO) mouse strain deficient in both miR-155 and miR-146a, we have also identified an epistatic relationship between these two miRNAs. DKO mice had defective T cell responses and tumor growth phenotypes similar to miR-155−/− mice. Further analysis of the T cell compartment revealed that miR-155 modulates IFNγ expression through a mechanism involving repression of Ship1. Our work reveals critical roles for miRNAs in the reciprocal regulation of CD4+ and CD8+ T cell-mediated antitumor immunity and demonstrates the dominant nature of miR-155 during its promotion of immune responses.
Graphical AbstractFigure optionsDownload as PowerPoint slideHighlights
► miR-155 promotes and miR-146a inhibits both CD4+ and CD8+ T cell antitumor responses
► DKO mice reveal epistasis between miR-155 and miR-146a during tumor immunity
► miR-155 regulation of IFNγ involves repression of its target Ship1 in T cells
Journal: - Volume 2, Issue 6, 27 December 2012, Pages 1697–1709