Lack of FcRn Impairs Natural Killer Cell Development and Functions in the Tumor Microenvironment

Front Immunol. 2018 Sep 28:9:2259. doi: 10.3389/fimmu.2018.02259. eCollection 2018.

Abstract

The neonatal Fc receptor (FcRn) is responsible for the recycling and transcytosis of IgG and albumin. FcRn level was found altered in cancer tissues and implicated in tumor immunosurveillance and neoplastic cell growth. However, the consequences of FcRn down-regulation in the anti-tumor immune response are not fully elucidated. By using the B16F10 experimental lung metastasis model in an FcRn-deficient microenvironment (FcRn-/- mice), we found lung metastasis associated with an abnormal natural killer (NK) cell phenotype. In FcRn-/- mice, NK cells were immature, as shown by their surface marker profile and their decreased ability to degranulate and synthesize interferon γ after chemical and IL-2 or IL-12, IL-15 and IL-18 activation. These new findings support the critical role of FcRn downregulation in the tumor microenvironment in anti-tumor immunity, via NK cell maturation and activation.

Keywords: CD107a; FcRn; IFN-γ; NK cells; anti-tumor immunity; fcgrt knock-out.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Degranulation
  • Cell Differentiation
  • Cell Line, Tumor
  • Disease Models, Animal
  • Down-Regulation
  • Histocompatibility Antigens Class I / metabolism*
  • Interferon-gamma / biosynthesis
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism*
  • Lung Neoplasms / pathology*
  • Lysosomal Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neoplasm Metastasis / pathology*
  • Receptors, Fc / metabolism*
  • Statistics, Nonparametric
  • Transcytosis
  • Tumor Microenvironment*

Substances

  • Histocompatibility Antigens Class I
  • IFNG protein, mouse
  • Lamp1 protein, mouse
  • Lysosomal Membrane Proteins
  • Receptors, Fc
  • Interferon-gamma
  • Fc receptor, neonatal