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Neonatal Fc receptor expression in dendritic cells mediates protective immunity against colorectal cancer.

Abstract
Cancers arising in mucosal tissues account for a disproportionately large fraction of malignancies. Immunoglobulin G (IgG) and the neonatal Fc receptor for IgG (FcRn) have an important function in the mucosal immune system that we have now shown extends to the induction of CD8(+) T cell-mediated antitumor immunity. We demonstrate that FcRn within dendritic cells (DCs) was critical for homeostatic activation of mucosal CD8(+) T cells that drove protection against the development of colorectal cancers and lung metastases. FcRn-mediated tumor protection was driven by DCs activation of endogenous tumor-reactive CD8(+) T cells via the cross-presentation of IgG complexed antigens (IgG IC), as well as the induction of cytotoxicity-promoting cytokine secretion, particularly interleukin-12, both of which were independently triggered by the FcRn-IgG IC interaction in murine and human DCs. FcRn thus has a primary role within mucosal tissues in activating local immune responses that are critical for priming efficient anti-tumor immunosurveillance.
AuthorsKristi Baker, Timo Rath, Magdalena B Flak, Janelle C Arthur, Zhangguo Chen, Jonathan N Glickman, Inti Zlobec, Eva Karamitopoulou, Matthew D Stachler, Robert D Odze, Wayne I Lencer, Christian Jobin, Richard S Blumberg
JournalImmunity (Immunity) Vol. 39 Issue 6 Pg. 1095-107 (Dec 12 2013) ISSN: 1097-4180 [Electronic] United States
PMID24290911 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2013 Elsevier Inc. All rights reserved.
Chemical References
  • Histocompatibility Antigens Class I
  • Receptors, Fc
  • Fc receptor, neonatal
Topics
  • Animals
  • Colorectal Neoplasms (genetics, immunology)
  • Dendritic Cells (immunology, metabolism)
  • Disease Models, Animal
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic
  • Histocompatibility Antigens Class I (genetics, metabolism)
  • Humans
  • Immunity (genetics)
  • Immunity, Active
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Fc (genetics, metabolism)

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