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.
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Authors | Kristi 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 |
Journal | Immunity
(Immunity)
Vol. 39
Issue 6
Pg. 1095-107
(Dec 12 2013)
ISSN: 1097-4180 [Electronic] United States |
PMID | 24290911
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2013 Elsevier Inc. All rights reserved. |
Chemical References |
- Histocompatibility Antigens Class I
- Receptors, Fc
- Fc receptor, neonatal
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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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