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 immuno-surveillance 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.