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
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TGFβ blocks IFNα/β release and tumor rejection in spontaneous mammary tumors
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Anmerkungen
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Nature communications. - 10, 1 (2019) , 4131, ISSN: 2041-1723
- Ereignis
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Veröffentlichung
- (wo)
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Freiburg
- (wer)
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Universität
- (wann)
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2019
- Urheber
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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
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10.1038/s41467-019-11998-w
- URN
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urn:nbn:de:bsz:25-freidok-1509091
- Rechteinformation
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Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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25.03.2025, 13:50 MEZ
Datenpartner
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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