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Nat Med. 2014 Nov;20(11):1301-9. doi: 10.1038/nm.3708. Epub 2014 Oct 26.

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

Author information

1
1] Gustave Roussy Cancer Campus, Villejuif, France. [2] INSERM, U1015, Villejuif, France. [3] Université Paris Saclay, Faculté de Médecine, Le Kremlin Bicêtre, France. [4] Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
2
1] Gustave Roussy Cancer Campus, Villejuif, France. [2] INSERM, U1015, Villejuif, France. [3] Université Paris Saclay, Faculté de Médecine, Le Kremlin Bicêtre, France.
3
1] Gustave Roussy Cancer Campus, Villejuif, France. [2] Université Paris Saclay, Faculté de Médecine, Le Kremlin Bicêtre, France. [3] INSERM, U848, Villejuif, France.
4
1] INSERM, U848, Villejuif, France. [2] Equipe 11 Labellisée par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. [3] Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
5
1] Gustave Roussy Cancer Campus, Villejuif, France. [2] Department of Biology and Pathology, Gustave Roussy Cancer Campus, Villejuif, France. [3] Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
6
Regina Elena National Cancer Institute, Rome, Italy.
7
1] Gustave Roussy Cancer Campus, Villejuif, France. [2] INSERM, U981, Villejuif, France.
8
1] Gustave Roussy Cancer Campus, Villejuif, France. [2] INSERM, U1015, Villejuif, France. [3] Transgene S.A., Illkirch-Graffenstaden, France.
9
Laboratory for Genomics and Immunoregulation, Life and Medical Sciences (LIMES), University of Bonn, Bonn, Germany.
10
Laboratory of Experimental Dermatology, Department of Dermatology, University Hospital Bonn, Bonn, Germany.
11
Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
12
1] SIB-Swiss Institute of Bioinformatics, Lausanne, Switzerland. [2] National Center of Competence in Research (NCCR) Molecular Oncology, Institut Suisse de Recherche Expérimentale sur le Cancer (ISREC), School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland. [3] Departement de Formation et Recherche, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
13
Department of Pathology, Centre Claudius Regaud, Toulouse, France.
14
1] Gustave Roussy Cancer Campus, Villejuif, France. [2] Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
15
1] Gustave Roussy Cancer Campus, Villejuif, France. [2] INSERM, U1015, Villejuif, France. [3] Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 507, Villejuif, France. [4] Department of Medical Oncology, Hôpital Pitie Salpetriere, Paris, France.
16
Department of Medical Oncology, Hôpital Pitie Salpetriere, Paris, France.
17
Yale School of Medicine, New Haven, Connecticut, USA.
18
1] Gustave Roussy Cancer Campus, Villejuif, France. [2] INSERM, U1015, Villejuif, France. [3] Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 507, Villejuif, France.
19
1] Gustave Roussy Cancer Campus, Villejuif, France. [2] Department of Biology and Pathology, Gustave Roussy Cancer Campus, Villejuif, France.
20
Department of Pathology, Jean Perrin Center, EA 4677 ERTICa, University of Auvergne, Clermont-Ferrand, France.
21
1] Department of Medical Oncology, Centre Georges-François Leclerc, Dijon, France. [2] INSERM, CRI-866 Faculty of Medicine, Dijon, France. [3] University of Burgundy, Dijon, France.
22
Université Paris Saclay, Faculté de Médecine, Le Kremlin Bicêtre, France.
23
San Raffaele University and Scientific Institute, Milan, Italy.
24
1] Center for Systems Biology, Massachusetts General Hospital, Boston, Massachusetts, USA. [2] Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts, USA.
25
Transgene S.A., Illkirch-Graffenstaden, France.
26
CNRS UMR5235, University Montpellier II, Place Eugène Bataillon, Montpellier, France.
27
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
28
Queensland Institute of Medical Research, Herston, Queensland, Australia.
29
1] Queensland Institute of Medical Research, Herston, Queensland, Australia. [2] School of Medicine, The University of Queensland, Herston, Queensland, Australia.
30
1] Gustave Roussy Cancer Campus, Villejuif, France. [2] Université Paris Saclay, Faculté de Médecine, Le Kremlin Bicêtre, France. [3] Department of Biology and Pathology, Gustave Roussy Cancer Campus, Villejuif, France. [4] Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France. [5] INSERM, U981, Villejuif, France.
31
1] Gustave Roussy Cancer Campus, Villejuif, France. [2] INSERM, U848, Villejuif, France. [3] Université Paris Descartes, Sorbonne Paris Cité, Paris, France. [4] Metabolomics Platform, Gustave Roussy Cancer Campus, Villejuif, France. [5] Pôle de Biologie, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
32
1] Gustave Roussy Cancer Campus, Villejuif, France. [2] Université Paris Saclay, Faculté de Médecine, Le Kremlin Bicêtre, France. [3] Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 507, Villejuif, France.

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.

PMID:
25344738
DOI:
10.1038/nm.3708
[Indexed for MEDLINE]

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