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

Antonella Sistigu, Takahiro Yamazaki, Erika Vacchelli, Kariman Chaba, David P. Enot, Julien Adam, Ilio Vitale, Aicha Goubar, Elisa E. Baracco, Catarina Remédios, Laetitia Fend, Dalil Hannani, Laetitia Aymeric, Yuting Ma, Mireia Niso-Santano, Oliver Kepp, Joachim L. Schultze, Thomas Tüting, Filippo Belardelli, Laura BracciValentina La Sorsa, Giovanna Ziccheddu, Paola Sestili, Francesca Urbani, Mauro Delorenzi, Magali Lacroix-Triki, Virginie Quidville, Rosa Conforti, Jean Philippe Spano, Lajos Pusztai, Vichnou Poirier-Colame, Suzette Delaloge, Frederique Penault-Llorca, Sylvain Ladoire, Laurent Arnould, Joanna Cyrta, Marie Charlotte Dessoliers, Alexander Eggermont, Marco E. Bianchi, Mikael Pittet, Camilla Engblom, Christina Pfirschke, Xavier Préville, Gilles Uzè, Robert D. Schreiber, Melvyn T. Chow, Mark J. Smyth, Enrico Proietti, Fabrice André, Guido Kroemer, Laurence Zitvogel

Research output: Contribution to journalArticlepeer-review

592 Scopus citations

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.

Original languageEnglish
Pages (from-to)1301-1309
Number of pages9
JournalNature medicine
Volume20
Issue number11
DOIs
StatePublished - Nov 1 2014

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