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

Diana Cadena Castaneda , Christine Dhommée , Thomas Baranek (1) , Emilie Dalloneau , Laurie Lajoie , Alexandre Valayer (1) , Christophe Arnoult , Marie-Véronique Demattéi , Delphine Fouquenet (1) , Christelle Parent , Nathalie Heuzé-Vourc'H , Valérie Gouilleux-Gruart

1 CEPR - Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100

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.

Mots clés: CD107a; FcRn; IFN-γ; NK cells; anti-tumor immunity; fcgrt knock-out

Domaines: Sciences du Vivant [q-bio]

Diana Cadena Castaneda, Christine Dhommée, Thomas Baranek, Emilie Dalloneau, Laurie Lajoie, et al.. Lack of FcRn Impairs Natural Killer Cell Development and Functions in the Tumor Microenvironment. Frontiers in Immunology, 2018, 9, ⟨10.3389/fimmu.2018.02259⟩. ⟨hal-03534425⟩