title: Neonatal Fc receptor expression in dendritic cells mediates protective immunity against colorectal cancer.
abstract: Cancers arising in mucosal tissues account for a disproportionately large fraction of malignancies. Immunoglobulin G (IgG) and the neonatal Fc receptor for IgG (FcRn) have an important function in the mucosal immune system that we have now shown extends to the induction of CD8(+) T cell-mediated antitumor immunity. We demonstrate that FcRn within dendritic cells (DCs) was critical for homeostatic activation of mucosal CD8(+) T cells that drove protection against the development of colorectal cancers and lung metastases. FcRn-mediated tumor protection was driven by DCs activation of endogenous tumor-reactive CD8(+) T cells via the cross-presentation of IgG complexed antigens (IgG IC), as well as the induction of cytotoxicity-promoting cytokine secretion, particularly interleukin-12, both of which were independently triggered by the FcRn-IgG IC interaction in murine and human DCs. FcRn thus has a primary role within mucosal tissues in activating local immune responses that are critical for priming efficient anti-tumor immunosurveillance.
authors.affiliation: Gastroenterology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Kristi
authors.initials: K
authors.lastname: Baker
authors.affiliation: Gastroenterology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Timo
authors.initials: T
authors.lastname: Rath
authors.affiliation: Gastroenterology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Magdalena B
authors.initials: MB
authors.lastname: Flak
authors.affiliation: Department of Medicine, Pharmacology and Immunology-Microbiology, University of North Carolina at Chapel Hill, NC 27599, USA.
authors.forename: Janelle C
authors.initials: JC
authors.lastname: Arthur
authors.affiliation: Gastroenterology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Zhangguo
authors.initials: Z
authors.lastname: Chen
authors.affiliation: GI Pathology, Caris Diagnostics, Caris Life Sciences, Newton, MA 02464, USA.
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Glickman
authors.affiliation: University of Bern, Institute of Pathology, Translational Research Unit, 3010 Bern, Switzerland.
authors.forename: Inti
authors.initials: I
authors.lastname: Zlobec
authors.affiliation: University of Bern, Institute of Pathology, Translational Research Unit, 3010 Bern, Switzerland.
authors.forename: Eva
authors.initials: E
authors.lastname: Karamitopoulou
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Stachler
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Odze
authors.affiliation: Harvard Digestive Diseases Center, Boston, MA 02115, USA; Division of Gastroenterology and Nutrition, Children's Hospital Boston and the Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Wayne I
authors.initials: WI
authors.lastname: Lencer
authors.affiliation: Department of Infectious Diseases & Pathology, College of Medicine, Department of Medicine, Division of Gastroenterology, Hepatology & Nutrition, Gainesville, FL 32611, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Jobin
authors.affiliation: Gastroenterology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Harvard Digestive Diseases Center, Boston, MA 02115, USA. Electronic address: rblumberg@partners.org.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Blumberg
mesh_terms: D000818:Animals; D015179:Colorectal Neoplasms / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007109:Immunity / Q000235:genetics*; D007110:Immunity, Active; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011961:Receptors, Fc / Q000235:genetics* / Q000378:metabolism*
chemical_list: D015395:Histocompatibility Antigens Class I; D011961:Receptors, Fc; C100688:Fc receptor, neonatal