Type I interferon is selectively required by dendritic cells for immune rejection of tumors.

2.50
HDL Handle:
http://hdl.handle.net/10033/226917
Title:
Type I interferon is selectively required by dendritic cells for immune rejection of tumors.
Authors:
Diamond, Mark S; Kinder, Michelle; Matsushita, Hirokazu; Mashayekhi, Mona; Dunn, Gavin P; Archambault, Jessica M; Lee, Hsiaoju; Arthur, Cora D; White, J Michael; Kalinke, Ulrich; Murphy, Kenneth M; Schreiber, Robert D
Abstract:
Cancer immunoediting is the process whereby the immune system suppresses neoplastic growth and shapes tumor immunogenicity. We previously reported that type I interferon (IFN-α/β) plays a central role in this process and that hematopoietic cells represent critical targets of type I IFN's actions. However, the specific cells affected by IFN-α/β and the functional processes that type I IFN induces remain undefined. Herein, we show that type I IFN is required to initiate the antitumor response and that its actions are temporally distinct from IFN-γ during cancer immunoediting. Using mixed bone marrow chimeric mice, we demonstrate that type I IFN sensitivity selectively within the innate immune compartment is essential for tumor-specific T cell priming and tumor elimination. We further show that mice lacking IFNAR1 (IFN-α/β receptor 1) in dendritic cells (DCs; Itgax-Cre(+)Ifnar1(f/f) mice) cannot reject highly immunogenic tumor cells and that CD8α(+) DCs from these mice display defects in antigen cross-presentation to CD8(+) T cells. In contrast, mice depleted of NK cells or mice that lack IFNAR1 in granulocytes and macrophage populations reject these tumors normally. Thus, DCs and specifically CD8α(+) DCs are functionally relevant targets of endogenous type I IFN during lymphocyte-mediated tumor rejection.
Affiliation:
Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
Citation:
Type I interferon is selectively required by dendritic cells for immune rejection of tumors. 2011, 208 (10):1989-2003 J. Exp. Med.
Journal:
The Journal of experimental medicine
Issue Date:
26-Sep-2011
URI:
http://hdl.handle.net/10033/226917
DOI:
10.1084/jem.20101158
PubMed ID:
21930769
Type:
Article
Language:
en
ISSN:
1540-9538
Appears in Collections:
Publications of the TwinCore unit experimental Infectionresearch(EXPI)

Full metadata record

DC FieldValueLanguage
dc.contributor.authorDiamond, Mark Sen_GB
dc.contributor.authorKinder, Michelleen_GB
dc.contributor.authorMatsushita, Hirokazuen_GB
dc.contributor.authorMashayekhi, Monaen_GB
dc.contributor.authorDunn, Gavin Pen_GB
dc.contributor.authorArchambault, Jessica Men_GB
dc.contributor.authorLee, Hsiaojuen_GB
dc.contributor.authorArthur, Cora Den_GB
dc.contributor.authorWhite, J Michaelen_GB
dc.contributor.authorKalinke, Ulrichen_GB
dc.contributor.authorMurphy, Kenneth Men_GB
dc.contributor.authorSchreiber, Robert Den_GB
dc.date.accessioned2012-05-31T13:54:38Z-
dc.date.available2012-05-31T13:54:38Z-
dc.date.issued2011-09-26-
dc.identifier.citationType I interferon is selectively required by dendritic cells for immune rejection of tumors. 2011, 208 (10):1989-2003 J. Exp. Med.en_GB
dc.identifier.issn1540-9538-
dc.identifier.pmid21930769-
dc.identifier.doi10.1084/jem.20101158-
dc.identifier.urihttp://hdl.handle.net/10033/226917-
dc.description.abstractCancer immunoediting is the process whereby the immune system suppresses neoplastic growth and shapes tumor immunogenicity. We previously reported that type I interferon (IFN-α/β) plays a central role in this process and that hematopoietic cells represent critical targets of type I IFN's actions. However, the specific cells affected by IFN-α/β and the functional processes that type I IFN induces remain undefined. Herein, we show that type I IFN is required to initiate the antitumor response and that its actions are temporally distinct from IFN-γ during cancer immunoediting. Using mixed bone marrow chimeric mice, we demonstrate that type I IFN sensitivity selectively within the innate immune compartment is essential for tumor-specific T cell priming and tumor elimination. We further show that mice lacking IFNAR1 (IFN-α/β receptor 1) in dendritic cells (DCs; Itgax-Cre(+)Ifnar1(f/f) mice) cannot reject highly immunogenic tumor cells and that CD8α(+) DCs from these mice display defects in antigen cross-presentation to CD8(+) T cells. In contrast, mice depleted of NK cells or mice that lack IFNAR1 in granulocytes and macrophage populations reject these tumors normally. Thus, DCs and specifically CD8α(+) DCs are functionally relevant targets of endogenous type I IFN during lymphocyte-mediated tumor rejection.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to The Journal of experimental medicineen_GB
dc.subject.meshAdoptive Transferen_GB
dc.subject.meshAnimalsen_GB
dc.subject.meshChimeraen_GB
dc.subject.meshCross-Primingen_GB
dc.subject.meshDendritic Cellsen_GB
dc.subject.meshGranulocytesen_GB
dc.subject.meshImmunity, Innateen_GB
dc.subject.meshInterferon Type Ien_GB
dc.subject.meshInterferon-gammaen_GB
dc.subject.meshKiller Cells, Naturalen_GB
dc.subject.meshLymphocyte Activationen_GB
dc.subject.meshMacrophagesen_GB
dc.subject.meshMiceen_GB
dc.subject.meshMice, Inbred C57BLen_GB
dc.subject.meshMice, Knockouten_GB
dc.subject.meshNeoplasmsen_GB
dc.subject.meshReceptor, Interferon alpha-betaen_GB
dc.subject.meshT-Lymphocyte Subsetsen_GB
dc.subject.meshT-Lymphocytes, Cytotoxicen_GB
dc.titleType I interferon is selectively required by dendritic cells for immune rejection of tumors.en
dc.typeArticleen
dc.contributor.departmentDepartment of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO, USA.en_GB
dc.identifier.journalThe Journal of experimental medicineen_GB

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