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

Baker, Kristi; Rath, Timo; Flak, Magdalena B.; Arthur, Janelle C.; Chen, Zhangguo; Glickman, Jonathan N.; Zlobec, Inti; Karamitopoulou, Evanthia; Stachler, Matthew D.; Odze, Robert D.; Lencer, Wayne I.; Jobin, Christian; Blumberg, Richard S. (2013). Neonatal Fc receptor expression in dendritic cells mediates protective immunity against colorectal cancer. Immunity, 39(6), pp. 1095-1107. Cell Press 10.1016/j.immuni.2013.11.003

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Zlobec, Inti, Karamitopoulou Diamantis, Evanthia

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1074-7613

Publisher:

Cell Press

Language:

English

Submitter:

Andrea Arnold

Date Deposited:

02 Apr 2014 15:27

Last Modified:

02 Mar 2023 23:24

Publisher DOI:

10.1016/j.immuni.2013.11.003

PubMed ID:

24290911

URI:

https://boris.unibe.ch/id/eprint/46152

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