TGFbeta blocks IFNalpha/beta release and tumor rejection in spontaneous mammary tumors : = TGFβ blocks IFNα/β release and tumor rejection in spontaneous mammary tumors

Abstract: 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 IFNα/β 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 IFNα/β production. Mechanistically, we identify TGFβ, which is abundant in spontaneous tumors, as a key molecule limiting this IFN-induced tumor regression by DMXAA. Finally, blocking TGFβ restores the production of IFNα 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 TGFβ

Object Details

• Alternative title: TGFβ blocks IFNα/β release and tumor rejection in spontaneous mammary tumors
• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Nature communications. - 10, 1 (2019) , 4131, ISSN: 2041-1723

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2019
• Creator: Guerin, Marion V. ; Regnier, Fabienne ; Feuillet, Vincent ; Vimeux, Lene ; Weiss, Julia Miriam ; Bismuth, Georges ; Altan-Bonnet, Grégoire ; Guilbert, Thomas ; Thoreau, Maxime ; Finisguerra, Veronica ; Donnadieu, Emmanuel ; Trautmann, Alain ; Bercovici, Nadège

Further information

• DOI: 10.1038/s41467-019-11998-w
• URN: urn:nbn:de:bsz:25-freidok-1509091
• Rights: Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 25.03.2025, 1:50 PM CET