Neonatal Fc Receptor Expression in Dendritic Cells Mediates Protective Immunity against Colorectal Cancer

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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

97 Citations (Scopus)

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+ Tcell-mediated antitumor immunity. We demonstrate that FcRn within dendritic cells (DCs) was critical for homeostatic activation of mucosal CD8+ Tcells 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+ Tcells 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.

Original languageEnglish
Pages (from-to)1095-1107
Number of pages13
JournalImmunity
Volume39
Issue number6
DOIs
Publication statusPublished - 12 Dec 2013

Keywords

  • Animals
  • Colorectal Neoplasms/genetics
  • Dendritic Cells/immunology
  • Disease Models, Animal
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic
  • Histocompatibility Antigens Class I/genetics
  • Humans
  • Immunity/genetics
  • Immunity, Active
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Fc/genetics

Fingerprint

Dive into the research topics of 'Neonatal Fc Receptor Expression in Dendritic Cells Mediates Protective Immunity against Colorectal Cancer'. Together they form a unique fingerprint.

Cite this