Journal
IMMUNITY
Volume 39, Issue 6, Pages 1095-1107Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2013.11.003
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Funding
- Canadian Institutes of Health Research
- Deutsche Forschungsgemeinschaft [RA 2040/1-1]
- Crohn's & Colitis Foundation of America
- High Pointe Foundation
- National Institutes of Health [T32 DK007737, DK73338, DK47700, DK53056, DK053162, DK088199, DK044319]
- Harvard Digestive Diseases Center NIH [P30DK034854]
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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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