title: Breast Cancer Cell-Derived GM-CSF Licenses Regulatory Th2 Induction by Plasmacytoid Predendritic Cells in Aggressive Disease Subtypes.
abstract: Reciprocal interactions between tumor cells and their microenvironment vitally impact tumor progression. In this study, we show that GM-CSF produced by primary breast tumor cells induced the activation of plasmacytoid predendritic cells (pDC), a cell type critical to anti-viral immunity. pDC that expressed the GM-CSF receptor were increased in breast tumors compared with noninvolved adjacent breast tissue. Tumor-activated pDC acquired naïve CD4(+) T-cell stimulatory capacity and promoted a regulatory Th2 response. Finally, the concomitant increase of GM-CSF and pDC was significantly associated with relatively more aggressive breast cancer subtypes. Our results characterize the first tumor-derived factor that can activate pDC to promote a regulatory Th2 response, with implications for therapeutic targeting of a tumor-immune axis of growing recognition in its significance to cancer.
authors.affiliation: INSERM U932, Institut Curie, Paris, France. Institut Curie, Department of Immunology, Paris, France.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ghirelli
authors.affiliation: UMR144 CNRS, Institut Curie, Paris, France. Institut Curie, Department of Surgical Oncology, Paris, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Reyal
authors.affiliation: INSERM U932, Institut Curie, Paris, France. Institut Curie, Department of Immunology, Paris, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Jeanmougin
authors.affiliation: INSERM U932, Institut Curie, Paris, France. Institut Curie, Department of Immunology, Paris, France.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Zollinger
authors.affiliation: INSERM U932, Institut Curie, Paris, France. Institut Curie, Department of Immunology, Paris, France.
authors.forename: Philémon
authors.initials: P
authors.lastname: Sirven
authors.affiliation: INSERM U932, Institut Curie, Paris, France. Institut Curie, Department of Immunology, Paris, France.
authors.forename: Paula
authors.initials: P
authors.lastname: Michea
authors.affiliation: Université Lyon 1, Lyon, France. INSERM U1052/CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France. Centre Léon Bérard, Lyon, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Caux
authors.affiliation: Université Lyon 1, Lyon, France. INSERM U1052/CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France. Centre Léon Bérard, Lyon, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bendriss-Vermare
authors.affiliation: INSERM U932, Institut Curie, Paris, France. Institut Curie, Department of Immunology, Paris, France.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Donnadieu
authors.affiliation: Institut Curie, Department of Pathology, Paris, France.
authors.forename: Martial
authors.initials: M
authors.lastname: Caly
authors.affiliation: Institut Curie, Department of Surgical Oncology, Paris, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Fourchotte
authors.affiliation: Institut Curie, Department of Pathology, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Vincent-Salomon
authors.affiliation: Institut Curie, Department of Pathology, Paris, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Sigal-Zafrani
authors.affiliation: Institut Curie, Department of Pathology, Paris, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Sastre-Garau
authors.affiliation: INSERM U932, Institut Curie, Paris, France. Institut Curie, Department of Immunology, Paris, France. Center of Clinical Investigations, Curie-IGR, Paris-Villejuif, France. vassili.soumelis@curie.fr.
authors.forename: Vassili
authors.initials: V
authors.lastname: Soumelis
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002470:Cell Survival / Q000276:immunology; D003110:Colonic Neoplasms / Q000276:immunology / Q000473:pathology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism* / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D061986:MCF-7 Cells; D009361:Neoplasm Invasiveness; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment / Q000187:drug effects / Q000276:immunology
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor