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Article Dans Une Revue Nature Medicine Année : 2014

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

Erika Vacchelli
Elisa E Baracco
  • Fonction : Auteur
Catarina Remédios
  • Fonction : Auteur
Laetitia Fend
  • Fonction : Auteur
Dalil Hannani
Oliver Kepp
Thomas Tüting
  • Fonction : Auteur
Filippo Belardelli
  • Fonction : Auteur
Valentina La Sorsa
  • Fonction : Auteur
Giovanna Ziccheddu
  • Fonction : Auteur
Paola Sestili
  • Fonction : Auteur
Francesca Urbani
  • Fonction : Auteur
Mauro Delorenzi
  • Fonction : Auteur
Virginie Quidville
  • Fonction : Auteur
Jean-Philippe Spano
Suzette Delaloge
Joanna Cyrta
  • Fonction : Auteur
Marie-Charlotte Dessoliers
  • Fonction : Auteur
Marco E Bianchi
  • Fonction : Auteur
Mikael Pittet
  • Fonction : Auteur
Xavier Préville
  • Fonction : Auteur
Robert D Schreiber
  • Fonction : Auteur
Melvyn T Chow
  • Fonction : Auteur
Mark J Smyth
  • Fonction : Auteur
Fabrice André
Guido Kroemer

Résumé

The immune system is routinely confronted with cell death resulting from the physiological turnover of renewable tissues, as well as from pathological insults of several types. We hypothesize the existence of a mechanism that allows the immune system to discriminate between physiological and pathological instances of cell death, but the factors that determine whether cellular demise is perceived as a neutral, tolerogenic or immunogenic event remain unclear 1. Infectious insults are accompanied by so-called microbe-associated molecular patterns (MAMPs), i.e., viral or bacterial products that activate immune cells through a panel of pattern-recognition receptors (PRRs) 2. Moreover, intracellular pathogens generally trigger adaptive mechanisms aimed toward the re-establishment of homeosta-sis, including the unfolded protein response (UPR) and autophagy 3,4. In mammals, MAMPs coupled to the activation of stress responses 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- and IFN- 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. npg
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Dates et versions

hal-02047408 , version 1 (06-03-2019)

Identifiants

Citer

Antonella Sistigu, Takahiro Yamazaki, Erika Vacchelli, Kariman Chaba, David Enot, et al.. Cancer cell–autonomous contribution of type I interferon signaling to the efficacy of chemotherapy. Nature Medicine, 2014, 20 (11), pp.1301-1309. ⟨10.1038/nm.3708⟩. ⟨hal-02047408⟩
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