Cancer cell-autonomous contribution of type I interferon signaling to the efficacy of chemotherapy

Sistigu, Antonella, Yamazaki, Takahiro, Vacchelli, Erika, Chaba, Kariman, Enot, David P., Adam, Julien, Vitale, Ilio, Goubar, Aicha, Baracco, Elisa E., Remedios, Catarina, Fend, Laetitia, Hannani, Dalil, Aymeric, Laetitia, Ma, Yuting, Niso-Santano, Mireia, Kepp, Oliver, Schultze, Joachim L., Tueting, Thomas, Belardelli, Filippo, Bracci, Laura, La Sorsa, Valentina, Ziccheddu, Giovanna, Sestili, Paola, Urbani, Francesca, Delorenzi, Mauro, Lacroix-Triki, Magali, Quidville, Virginie, Conforti, Rosa, Spano, Jean-Philippe, Pusztai, Lajos, Poirier-Colame, Vichnou, Delaloge, Suzette, Penault-Llorca, Frederique, Ladoire, Sylvain, Arnould, Laurent, Cyrta, Joanna, Dessoliers, Marie-Charlotte, Eggermont, Alexander, Bianchi, Marco E., Pittet, Mikael, Engblom, Camilla, Pfirschke, Christina, Preville, Xavier, Uze, Gilles, Schreiber, Robert D., Chow, Melvyn T., Smyth, Mark J., Proietti, Enrico, Andre, Fabrice, Kroemer, Guido and Zitvogel, Laurence (2014) Cancer cell-autonomous contribution of type I interferon signaling to the efficacy of chemotherapy. Nature Medicine, 20 11: 1301-1309. doi:10.1038/nm.3708

Author Sistigu, Antonella
Yamazaki, Takahiro
Vacchelli, Erika
Chaba, Kariman
Enot, David P.
Adam, Julien
Vitale, Ilio
Goubar, Aicha
Baracco, Elisa E.
Remedios, Catarina
Fend, Laetitia
Hannani, Dalil
Aymeric, Laetitia
Ma, Yuting
Niso-Santano, Mireia
Kepp, Oliver
Schultze, Joachim L.
Tueting, Thomas
Belardelli, Filippo
Bracci, Laura
La Sorsa, Valentina
Ziccheddu, Giovanna
Sestili, Paola
Urbani, Francesca
Delorenzi, Mauro
Lacroix-Triki, Magali
Quidville, Virginie
Conforti, Rosa
Spano, Jean-Philippe
Pusztai, Lajos
Poirier-Colame, Vichnou
Delaloge, Suzette
Penault-Llorca, Frederique
Ladoire, Sylvain
Arnould, Laurent
Cyrta, Joanna
Dessoliers, Marie-Charlotte
Eggermont, Alexander
Bianchi, Marco E.
Pittet, Mikael
Engblom, Camilla
Pfirschke, Christina
Preville, Xavier
Uze, Gilles
Schreiber, Robert D.
Chow, Melvyn T.
Smyth, Mark J.
Proietti, Enrico
Andre, Fabrice
Kroemer, Guido
Zitvogel, Laurence
Title Cancer cell-autonomous contribution of type I interferon signaling to the efficacy of chemotherapy
Journal name Nature Medicine   Check publisher's open access policy
ISSN 1078-8956
Publication date 2014-11
Year available 2014
Sub-type Article (original research)
DOI 10.1038/nm.3708
Open Access Status
Volume 20
Issue 11
Start page 1301
End page 1309
Total pages 9
Place of publication New York NY United States
Publisher Nature Publishing Group
Collection year 2015
Language eng
Abstract Some of the anti-neoplastic effects of anthracyclines in mice originate from the induction of innate and T cell–mediated anticancer immune responses. Here we demonstrate that anthracyclines stimulate the rapid production of type I interferons (IFNs) by malignant cells after activation of the endosomal pattern recognition receptor Toll-like receptor 3 (TLR3). By binding to IFN-α and IFN-β receptors (IFNARs) on neoplastic cells, type I IFNs trigger autocrine and paracrine circuitries that result in the release of chemokine (C-X-C motif) ligand 10 (CXCL10). Tumors lacking Tlr3 or Ifnar failed to respond to chemotherapy unless type I IFN or Cxcl10, respectively, was artificially supplied. Moreover, a type I IFN–related signature predicted clinical responses to anthracycline-based chemotherapy in several independent cohorts of patients with breast carcinoma characterized by poor prognosis. Our data suggest that anthracycline-mediated immune responses mimic those induced by viral pathogens. We surmise that such 'viral mimicry' constitutes a hallmark of successful chemotherapy.
Keyword Toll like receptor 3
Double stranded RNA
Breast cancer
Immune responses
Anticancer chemotherapy
Dendritic cells
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
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