Frontiers in Immunology (Sep 2018)

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

  • Diana Cadena Castaneda,
  • Diana Cadena Castaneda,
  • Christine Dhommée,
  • Christine Dhommée,
  • Thomas Baranek,
  • Thomas Baranek,
  • Emilie Dalloneau,
  • Emilie Dalloneau,
  • Laurie Lajoie,
  • Laurie Lajoie,
  • Alexandre Valayer,
  • Alexandre Valayer,
  • Christophe Arnoult,
  • Christophe Arnoult,
  • Marie-Véronique Demattéi,
  • Marie-Véronique Demattéi,
  • Delphine Fouquenet,
  • Delphine Fouquenet,
  • Christelle Parent,
  • Christelle Parent,
  • Nathalie Heuzé-Vourc'h,
  • Nathalie Heuzé-Vourc'h,
  • Valérie Gouilleux-Gruart,
  • Valérie Gouilleux-Gruart

DOI
https://doi.org/10.3389/fimmu.2018.02259
Journal volume & issue
Vol. 9

Abstract

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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.

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