| First Author | Guerin MV | Year | 2019 |
| Journal | Nat Commun | Volume | 10 |
| Issue | 1 | Pages | 4131 |
| PubMed ID | 31511510 | Mgi Jnum | J:279467 |
| Mgi Id | MGI:6362504 | Doi | 10.1038/s41467-019-11998-w |
| Citation | Guerin MV, et al. (2019) TGFbeta blocks IFNalpha/beta release and tumor rejection in spontaneous mammary tumors. Nat Commun 10(1):4131 |
| abstractText | Type I interferons (IFN) are being rediscovered as potent anti-tumoral agents. Activation of the STimulator of INterferon Genes (STING) by DMXAA (5,6-dimethylxanthenone-4-acetic acid) can induce strong production of IFNalpha/beta and rejection of transplanted primary tumors. In the present study, we address whether targeting STING with DMXAA also leads to the regression of spontaneous MMTV-PyMT mammary tumors. We show that these tumors are refractory to DMXAA-induced regression. This is due to a blockade in the phosphorylation of IRF3 and the ensuing IFNalpha/beta production. Mechanistically, we identify TGFbeta, which is abundant in spontaneous tumors, as a key molecule limiting this IFN-induced tumor regression by DMXAA. Finally, blocking TGFbeta restores the production of IFNalpha by activated MHCII(+) tumor-associated macrophages, and enables tumor regression induced by STING activation. On the basis of these findings, we propose that type I IFN-dependent cancer therapies could be greatly improved by combinations including the blockade of TGFbeta. |
