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

Immunity. 2013 Dec 12;39(6):1095-107. doi: 10.1016/j.immuni.2013.11.003. Epub 2013 Nov 27.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Histocompatibility Antigens Class I
  • Receptors, Fc
  • Fc receptor, neonatal