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

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

doi:10.3389/fimmu.2018.02259

Diana Cadena Castaneda, Marie-Véronique Demattéi + Show 10 more

Open Access

https://doi.org/10.3389/fimmu.2018.02259

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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.

Highlights

IntroductionThe neonatal Fc receptor (FcRn) is a member of the IgG-Fc receptor family comprising type I (e.g., “classical” FcγRs) and type II (e.g., non-classical FcR: FcRn, TRIM21) receptors [1,2,3]
The neonatal Fc receptor (FcRn) is a member of the IgG-Fc receptor family comprising type I (e.g., “classical” FcγRs) and type II receptors [1,2,3]
To dissect the role of FcRn in anti-tumor immunity, we used the well-characterized syngeneic B16F10 experimental lung metastasis mouse model [15, 16]

Summary

Introduction

The neonatal Fc receptor (FcRn) is a member of the IgG-Fc receptor family comprising type I (e.g., “classical” FcγRs) and type II (e.g., non-classical FcR: FcRn, TRIM21) receptors [1,2,3]. The structure, expression and functions of this IgG-Fc receptors have been extensively rewiewed regarding their major role in the regulation of immune responses [4]. FcRn is an MHC class I-related molecule consisting of a heavy chain associated with β2-microglobulin molecule, wellknown for its role in regulating IgG and albumin homeostasis [5]. FcRn expression is ubiquitous within organs and tissues, with high expression in endothelial and epithelial cells [9]. It is expressed by hematopoietic cells, in particular macrophages/monocytes and dendritic cells (DCs) [10]. The expression of FcRn in antigenpresenting cells is connected to its implication in the humoral immune response, via an immune complex presentation [11]

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