| First Author | Salerno F | Year | 2019 |
| Journal | Oncoimmunology | Volume | 8 |
| Issue | 2 | Pages | e1532762 |
| PubMed ID | 30713785 | Mgi Jnum | J:313662 |
| Mgi Id | MGI:6791273 | Doi | 10.1080/2162402X.2018.1532762 |
| Citation | Salerno F, et al. (2019) Critical role of post-transcriptional regulation for IFN-gamma in tumor-infiltrating T cells. Oncoimmunology 8(2):e1532762 |
| abstractText | Protective T cell responses against tumors require the production of Interferon gamma (IFN-gamma). However, tumor-infiltrating T cells (TILs) gradually lose their capacity to produce IFN-gamma and therefore fail to clear malignant cells. Dissecting the underlying mechanisms that block cytokine production is thus key for improving T cell products. Here we show that although TILs express substantial levels of Ifng mRNA, post-transcriptional mechanisms impede the production of IFN-gamma protein due to loss of mRNA stability. CD28 triggering, but not PD1 blocking antibodies, effectively restores the stability of Ifng mRNA. Intriguingly, TILs devoid of AU-rich elements within the 3'untranslated region maintain stabilized Ifng mRNA and produce more IFN-gamma protein than wild-type TILs. This sustained IFN-gamma production translates into effective suppression of tumor outgrowth, which is almost exclusively mediated by direct effects on the tumor cells. We therefore conclude that post-transcriptional mechanisms could be modulated to potentiate effective T cell therapies in cancer. |
