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Article: A crucial role for dendritic cell (DC) IL-10 in inhibiting successful DC-based immunotherapy: Superior antitumor immunity against hepatocellular carcinoma evoked by DC devoid of IL-101

TitleA crucial role for dendritic cell (DC) IL-10 in inhibiting successful DC-based immunotherapy: Superior antitumor immunity against hepatocellular carcinoma evoked by DC devoid of IL-101
Authors
Issue Date2007
PublisherAmerican Association of Immunologists. The Journal's web site is located at http://www.jimmunol.org
Citation
Journal of Immunology, 2007, v. 179 n. 9, p. 6009-6015 How to Cite?
Abstract
The dendritic cell (DC)-based tumor immunotherapy has been a new promise of cure for cancer patients, but animal studies and clinical trials have thus far only shown limited success, especially in treating established tumors. Certain immunosuppressive mechanisms triggered by tumor cells or the derivatives are believed to be a major obstacle. We studied the role of DC-derived IL-10 and its negative impact on vaccine efficacy in mouse models. Liver tumor cells were injected via the portal vein, giving rise to disseminated intrahepatic tumors, or s.c. to form solid but extrahepatic tumors. Bone marrow-derived DCs were generated from normal or IL-10-deficient mice and used as the vector to deliver tumor Ags. We demonstrate here that DCs devoid of IL-10, a potent immunosuppressive cytokine, are superior over conventional DCs in triggering antitumor immunity. The IL-10 -/-DCs were highly immunogenic, expressed enhanced levels of surface MHC class II molecules, and secreted increased amounts of Th1-related cytokines. By inducing tumor-specific killing and through the establishment of immunological memory, the vaccines delivered by IL-10 -/-DCs could evoke strong therapeutic and protective immunity against hepatocellular carcinoma in the mouse models. These findings will have great clinical impact once being translated into the treatment of malignant, and potentially infectious, diseases in humans. Copyright © 2007 by The American Association of Immunologists, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/148542
ISSN
2013 Impact Factor: 5.362
ISI Accession Number ID
References

 

Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine
  2. Hammersmith Hospital
  3. Imperial College London
  4. University of Cambridge
  5. Xiangya School of Medicine
DC FieldValueLanguage
dc.contributor.authorChen, YXen_HK
dc.contributor.authorMan, Ken_HK
dc.contributor.authorGuang, SLen_HK
dc.contributor.authorChen, Yen_HK
dc.contributor.authorSun, BSen_HK
dc.contributor.authorCheng, Qen_HK
dc.contributor.authorOn, HWen_HK
dc.contributor.authorLo, CKen_HK
dc.contributor.authorNg, IOen_HK
dc.contributor.authorLi, CCen_HK
dc.contributor.authorLau, GKen_HK
dc.contributor.authorLin, CLSen_HK
dc.contributor.authorHuang, Fen_HK
dc.contributor.authorHuang, FPen_HK
dc.date.accessioned2012-05-29T06:13:37Z-
dc.date.available2012-05-29T06:13:37Z-
dc.date.issued2007en_HK
dc.identifier.citationJournal of Immunology, 2007, v. 179 n. 9, p. 6009-6015en_HK
dc.identifier.issn0022-1767en_HK
dc.identifier.urihttp://hdl.handle.net/10722/148542-
dc.description.abstractThe dendritic cell (DC)-based tumor immunotherapy has been a new promise of cure for cancer patients, but animal studies and clinical trials have thus far only shown limited success, especially in treating established tumors. Certain immunosuppressive mechanisms triggered by tumor cells or the derivatives are believed to be a major obstacle. We studied the role of DC-derived IL-10 and its negative impact on vaccine efficacy in mouse models. Liver tumor cells were injected via the portal vein, giving rise to disseminated intrahepatic tumors, or s.c. to form solid but extrahepatic tumors. Bone marrow-derived DCs were generated from normal or IL-10-deficient mice and used as the vector to deliver tumor Ags. We demonstrate here that DCs devoid of IL-10, a potent immunosuppressive cytokine, are superior over conventional DCs in triggering antitumor immunity. The IL-10 -/-DCs were highly immunogenic, expressed enhanced levels of surface MHC class II molecules, and secreted increased amounts of Th1-related cytokines. By inducing tumor-specific killing and through the establishment of immunological memory, the vaccines delivered by IL-10 -/-DCs could evoke strong therapeutic and protective immunity against hepatocellular carcinoma in the mouse models. These findings will have great clinical impact once being translated into the treatment of malignant, and potentially infectious, diseases in humans. Copyright © 2007 by The American Association of Immunologists, Inc.en_HK
dc.languageengen_US
dc.publisherAmerican Association of Immunologists. The Journal's web site is located at http://www.jimmunol.orgen_HK
dc.relation.ispartofJournal of Immunologyen_HK
dc.subject.meshAnimalsen_US
dc.subject.meshCancer Vaccinesen_US
dc.subject.meshCarcinoma, Hepatocellular - Immunology - Pathology - Therapyen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshDendritic Cells - Immunologyen_US
dc.subject.meshDisease Models, Animalen_US
dc.subject.meshImmunologic Memory - Immunologyen_US
dc.subject.meshImmunotherapyen_US
dc.subject.meshInterleukin-10 - Deficiency - Genetics - Immunology - Metabolismen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Knockouten_US
dc.subject.meshNeoplasm Transplantationen_US
dc.subject.meshPhenotypeen_US
dc.titleA crucial role for dendritic cell (DC) IL-10 in inhibiting successful DC-based immunotherapy: Superior antitumor immunity against hepatocellular carcinoma evoked by DC devoid of IL-101en_HK
dc.typeArticleen_HK
dc.identifier.emailMan, K: kwanman@hkucc.hku.hken_HK
dc.identifier.emailLo, CK: cklo@pathology.hku.hken_HK
dc.identifier.emailNg, IOL: iolng@hkucc.hku.hken_HK
dc.identifier.emailLi, CC: chanlc@hkucc.hku.hk-
dc.identifier.authorityMan, K=rp00417en_HK
dc.identifier.authorityNg, IO=rp00335en_HK
dc.identifier.authorityLi, CC=rp00373en_HK
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.pmid17947674en_US
dc.identifier.scopuseid_2-s2.0-38449083230en_HK
dc.identifier.hkuros151259-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-38449083230&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume179en_HK
dc.identifier.issue9en_HK
dc.identifier.spage6009en_HK
dc.identifier.epage6015en_HK
dc.identifier.isiWOS:000250388000045-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridChen, YX=37095401100en_HK
dc.identifier.scopusauthoridMan, K=7101754072en_HK
dc.identifier.scopusauthoridGuang, SL=26027904800en_HK
dc.identifier.scopusauthoridChen, Y=23471877400en_HK
dc.identifier.scopusauthoridSun, BS=23101636500en_HK
dc.identifier.scopusauthoridCheng, Q=16024087700en_HK
dc.identifier.scopusauthoridOn, HW=26028087900en_HK
dc.identifier.scopusauthoridLo, CK=7401771543en_HK
dc.identifier.scopusauthoridNg, IO=7102753722en_HK
dc.identifier.scopusauthoridLi, CC=7403540707en_HK
dc.identifier.scopusauthoridLau, GK=7102301257en_HK
dc.identifier.scopusauthoridLin, CLS=37099293900en_HK
dc.identifier.scopusauthoridHuang, F=55238930200en_HK
dc.identifier.scopusauthoridHuang, FP=35358178100en_HK
dc.customcontrol.immutablesml 130626-

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