AUTHOR=Castaneda Diana Cadena , Dhommée Christine , Baranek Thomas , Dalloneau Emilie , Lajoie Laurie , Valayer Alexandre , Arnoult Christophe , Demattéi Marie-Véronique , Fouquenet Delphine , Parent Christelle , Heuzé-Vourc'h Nathalie , Gouilleux-Gruart Valérie TITLE=Lack of FcRn Impairs Natural Killer Cell Development and Functions in the Tumor Microenvironment JOURNAL=Frontiers in Immunology VOLUME=Volume 9 - 2018 YEAR=2018 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.02259 DOI=10.3389/fimmu.2018.02259 ISSN=1664-3224 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.