| First Author | Huffaker TB | Year | 2012 |
| Journal | Cell Rep | Volume | 2 |
| Issue | 6 | Pages | 1697-709 |
| PubMed ID | 23200854 | Mgi Jnum | J:196336 |
| Mgi Id | MGI:5487741 | Doi | 10.1016/j.celrep.2012.10.025 |
| Citation | Huffaker TB, et al. (2012) Epistasis between microRNAs 155 and 146a during T cell-mediated antitumor immunity. Cell Rep 2(6):1697-709 |
| abstractText | An 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 gamma (IFNgamma) 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 IFNgamma 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. |
