| First Author | Kosaka A | Year | 2015 |
| Journal | Biochem Biophys Res Commun | Volume | 458 |
| Issue | 3 | Pages | 549-54 |
| PubMed ID | 25677619 | Mgi Jnum | J:220491 |
| Mgi Id | MGI:5634868 | Doi | 10.1016/j.bbrc.2015.02.003 |
| Citation | Kosaka A, et al. (2015) Transgene-derived overexpression of miR-17-92 in CD8+ T-cells confers enhanced cytotoxic activity. Biochem Biophys Res Commun 458(3):549-54 |
| abstractText | MicroRNAs (miRs) play important roles in regulation of a variety of cell functions, including immune responses. We have previously demonstrated that miR-17-92 expression in T-cells enhances Th1 phenotype and provides a long-term protection against glioblastoma when co-expressed as a transgene in T-cells along with a chimeric antigen receptor. To further elucidate the function of miR-17-92 in tumor antigen-specific CD8(+) T-cells, we generated transgenic (Tg) mice in which CD8(+) T-cells overexpress transgene-derived miR-17-92 under the lck promoter as well as T-cell receptor specific for human gp10025-33 (Pmel-1) (miR-17-92/Pmel-Tg). CD8(+) T-cells from miR-17-92/Pmel-Tg mice demonstrated enhanced interferon (IFN)-gamma production and cytotoxicity in response to the cognate antigen compared with those from control Pmel-Tg mice without the transgene for miR-17-92. In addition, miR-17-92/Pmel-Tg mouse-derived CD8(+)CD44(+) T-cells demonstrated increased frequencies of cells with memory phenotypes and IFN-gamma production. We also found that miR-17-92/Pmel-Tg-derived CD8(+) T-cells expressed decreased levels of transforming growth factor (TGF)-beta type II receptor (TGFBR2) on their surface, thereby resisting against suppressive effects of TGF-beta1. Our findings suggest that engineering of tumor antigen-specific CD8(+) T-cells to express miR-17-92 may improve the potency of cancer immunotherapy. |
