Inducing Tumor Immunity through the Selective Engagement of Activating Fcγ Receptors on Dendritic Cells

Induction of tumor-specific immunity requires that dendritic cells (DCs) efficiently capture and present tumor antigens to result in the expansion and activation of tumor-specific cytotoxic T cells. The transition from antigen capture to T cell stimulation requires a maturation signal; in its absenc...

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Main Authors:	Kalergis, Alexis M., Ravetch, Jeffrey V.
Format:	Online
Language:	English
Published:	The Rockefeller University Press 2002
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193555/

id	pubmed-2193555
recordtype	oai_dc
spelling	pubmed-21935552008-04-14 Inducing Tumor Immunity through the Selective Engagement of Activating Fcγ Receptors on Dendritic Cells Kalergis, Alexis M. Ravetch, Jeffrey V. Brief Definitive Report Induction of tumor-specific immunity requires that dendritic cells (DCs) efficiently capture and present tumor antigens to result in the expansion and activation of tumor-specific cytotoxic T cells. The transition from antigen capture to T cell stimulation requires a maturation signal; in its absence tolerance, rather than immunity may develop. While immune complexes (ICs) are able to enhance antigen capture, they can be poor at inducing DC maturation, naive T cell activation and protective immunity. We now demonstrate that interfering with the inhibitory signal delivered by FcγRIIB on DCs converts ICs to potent maturation agents and results in T cell activation. Applying this approach to immunization with DCs pulsed ex-vivo with ICs, we have generated antigen-specific CD8+ T cells in vivo and achieved efficient protective immunity in a murine melanoma model. These data imply that ICs may normally function to maintain tolerance through the binding to inhibitory FcγRs on DCs, but they can be converted to potent immunogenic stimuli by selective engagement of activating FcγRs. This mechanism suggests a novel approach to the development of tumor vaccines. The Rockefeller University Press 2002-06-17 /pmc/articles/PMC2193555/ /pubmed/12070293 http://dx.doi.org/10.1084/jem.20020338 Text en Copyright © 2002, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Kalergis, Alexis M. Ravetch, Jeffrey V.
spellingShingle	Kalergis, Alexis M. Ravetch, Jeffrey V. Inducing Tumor Immunity through the Selective Engagement of Activating Fcγ Receptors on Dendritic Cells
author_facet	Kalergis, Alexis M. Ravetch, Jeffrey V.
author_sort	Kalergis, Alexis M.
title	Inducing Tumor Immunity through the Selective Engagement of Activating Fcγ Receptors on Dendritic Cells
title_short	Inducing Tumor Immunity through the Selective Engagement of Activating Fcγ Receptors on Dendritic Cells
title_full	Inducing Tumor Immunity through the Selective Engagement of Activating Fcγ Receptors on Dendritic Cells
title_fullStr	Inducing Tumor Immunity through the Selective Engagement of Activating Fcγ Receptors on Dendritic Cells
title_full_unstemmed	Inducing Tumor Immunity through the Selective Engagement of Activating Fcγ Receptors on Dendritic Cells
title_sort	inducing tumor immunity through the selective engagement of activating fcγ receptors on dendritic cells
description	Induction of tumor-specific immunity requires that dendritic cells (DCs) efficiently capture and present tumor antigens to result in the expansion and activation of tumor-specific cytotoxic T cells. The transition from antigen capture to T cell stimulation requires a maturation signal; in its absence tolerance, rather than immunity may develop. While immune complexes (ICs) are able to enhance antigen capture, they can be poor at inducing DC maturation, naive T cell activation and protective immunity. We now demonstrate that interfering with the inhibitory signal delivered by FcγRIIB on DCs converts ICs to potent maturation agents and results in T cell activation. Applying this approach to immunization with DCs pulsed ex-vivo with ICs, we have generated antigen-specific CD8+ T cells in vivo and achieved efficient protective immunity in a murine melanoma model. These data imply that ICs may normally function to maintain tolerance through the binding to inhibitory FcγRs on DCs, but they can be converted to potent immunogenic stimuli by selective engagement of activating FcγRs. This mechanism suggests a novel approach to the development of tumor vaccines.
publisher	The Rockefeller University Press
publishDate	2002
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193555/
_version_	1611431164923346944

Inducing Tumor Immunity through the Selective Engagement of Activating Fcγ Receptors on Dendritic Cells

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