title: IgE/FcεRI-Mediated Antigen Cross-Presentation by Dendritic Cells Enhances Anti-Tumor Immune Responses.
abstract: Epidemiologic studies discovered an inverse association between immunoglobulin E (IgE)-mediated allergies and cancer, implying tumor-protective properties of IgE. However, the underlying immunologic mechanisms remain poorly understood. Antigen cross-presentation by dendritic cells (DCs) is of key importance for anti-tumor immunity because it induces the generation of cytotoxic CD8+T lymphocytes (CTLs) with specificity for tumor antigens. We demonstrate that DCs use IgE and FcεRI, the high-affinity IgE receptor, for cross-presentation and priming of CTLs in response to free soluble antigen at low doses. Importantly, IgE/FcεRI-mediated cross-presentation is a distinct receptor-mediated pathway because it does not require MyD88 signals or IL-12 induction in DCs. Using passive immunization with tumor antigen-specific IgE and DC-based vaccination experiments, we demonstrate that IgE-mediated cross-presentation significantly improves anti-tumor immunity and induces memory responses in vivo. Our findings suggest a cellular mechanism for the tumor-protective features of IgE and expand the known physiological functions of this immunoglobulin.
authors.affiliation: Division of Gastroenterology and Nutrition, Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Platzer
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: Kutlu G
authors.initials: KG
authors.lastname: Elpek
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: Viviana
authors.initials: V
authors.lastname: Cremasco
authors.affiliation: Division of Gastroenterology, Brigham and Women's Hospital and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Kristi
authors.initials: K
authors.lastname: Baker
authors.affiliation: Division of Gastroenterology and Nutrition, Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Madeleine M
authors.initials: MM
authors.lastname: Stout
authors.affiliation: Division of Gastroenterology and Nutrition, Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Schultz
authors.affiliation: Division of Gastroenterology and Nutrition, Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Dehlink
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
authors.forename: Kai-Ting C
authors.initials: KC
authors.lastname: Shade
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Anthony
authors.affiliation: Division of Gastroenterology, Brigham and Women's Hospital and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Blumberg
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: Shannon J
authors.initials: SJ
authors.lastname: Turley
authors.affiliation: Division of Gastroenterology and Nutrition, Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA. Electronic address: edda.fiebiger@childrens.harvard.edu.
authors.forename: Edda
authors.initials: E
authors.lastname: Fiebiger