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

Weitere Titel
TGFβ blocks IFNα/β release and tumor rejection in spontaneous mammary tumors
Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch
Anmerkungen
Nature communications. - 10, 1 (2019) , 4131, ISSN: 2041-1723

Ereignis
Veröffentlichung
(wo)
Freiburg
(wer)
Universität
(wann)
2019
Urheber
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

DOI
10.1038/s41467-019-11998-w
URN
urn:nbn:de:bsz:25-freidok-1509091
Rechteinformation
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Letzte Aktualisierung
25.03.2025, 13:50 MEZ

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Beteiligte

  • 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
  • Universität

Entstanden

  • 2019

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