| Literature DB >> 25344738 |
Antonella Sistigu1, Takahiro Yamazaki2, Erika Vacchelli3, Kariman Chaba4, David P Enot4, Julien Adam5, Ilio Vitale6, Aicha Goubar7, Elisa E Baracco3, Catarina Remédios2, Laetitia Fend8, Dalil Hannani2, Laetitia Aymeric2, Yuting Ma3, Mireia Niso-Santano3, Oliver Kepp3, Joachim L Schultze9, Thomas Tüting10, Filippo Belardelli11, Laura Bracci11, Valentina La Sorsa11, Giovanna Ziccheddu11, Paola Sestili11, Francesca Urbani11, Mauro Delorenzi12, Magali Lacroix-Triki13, Virginie Quidville14, Rosa Conforti15, Jean-Philippe Spano16, Lajos Pusztai17, Vichnou Poirier-Colame18, Suzette Delaloge19, Frederique Penault-Llorca20, Sylvain Ladoire21, Laurent Arnould21, Joanna Cyrta19, Marie-Charlotte Dessoliers7, Alexander Eggermont22, Marco E Bianchi23, Mikael Pittet24, Camilla Engblom24, Christina Pfirschke24, Xavier Préville25, Gilles Uzè26, Robert D Schreiber27, Melvyn T Chow28, Mark J Smyth29, Enrico Proietti11, Fabrice André30, Guido Kroemer31, Laurence Zitvogel32.
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.Entities:
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Year: 2014 PMID： 25344738 DOI： 10.1038/nm.3708
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440