Virus-induced tumor inflammation facilitates effective DC cancer immunotherapy in a Treg-dependent manner in mice.

2.50
Hdl Handle:
http://hdl.handle.net/10033/203309
Title:
Virus-induced tumor inflammation facilitates effective DC cancer immunotherapy in a Treg-dependent manner in mice.
Authors:
Woller, Norman; Knocke, Sarah; Mundt, Bettina; Gürlevik, Engin; Strüver, Nina; Kloos, Arnold; Boozari, Bita; Schache, Peter; Manns, Michael P; Malek, Nisar P; Sparwasser, Tim; Zender, Lars; Wirth, Thomas C; Kubicka, Stefan; Kühnel, Florian
Abstract:
Vaccination using DCs pulsed with tumor lysates or specific tumor-associated peptides has so far yielded limited clinical success for cancer treatment, due mainly to the low immunogenicity of tumor-associated antigens. In this study, we have identified intratumoral virus-induced inflammation as a precondition for effective antitumor DC vaccination in mice. Administration of a tumor-targeted DC vaccine during ongoing virus-induced tumor inflammation, a regimen referred to as oncolysis-assisted DC vaccination (ODC), elicited potent antitumoral CD8+ T cell responses. This potent effect was not replicated by TLR activation outside the context of viral infection. ODC-elicited immune responses mediated marked tumor regression and successful eradication of preestablished lung colonies, an essential prerequisite for potentially treating metastatic cancers. Unexpectedly, depletion of Tregs during ODC did not enhance therapeutic efficacy; rather, it abrogated antitumor cytotoxicity. This phenomenon could be attributed to a compensatory induction of myeloid-derived suppressor cells in Treg-depleted and thus vigorously inflamed tumors, which prevented ODC-mediated immune responses. Consequently, Tregs are not only general suppressors of immune responses, but are essential for the therapeutic success of multimodal and temporally fine-adjusted vaccination strategies. Our results highlight tumor-targeting, replication-competent viruses as attractive tools for eliciting effective antitumor responses upon DC vaccination.
Affiliation:
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Citation:
Virus-induced tumor inflammation facilitates effective DC cancer immunotherapy in a Treg-dependent manner in mice. 2011, 121 (7):2570-82 J. Clin. Invest.
Journal:
The Journal of clinical investigation
Issue Date:
1-Jul-2011
URI:
http://hdl.handle.net/10033/203309
DOI:
10.1172/JCI45585
PubMed ID:
21646722
Type:
Article
Language:
en
ISSN:
1558-8238
Appears in Collections:
publications of the TwinCore unit Infection immunology

Full metadata record

DC FieldValue Language
dc.contributor.authorWoller, Normanen
dc.contributor.authorKnocke, Sarahen
dc.contributor.authorMundt, Bettinaen
dc.contributor.authorGürlevik, Enginen
dc.contributor.authorStrüver, Ninaen
dc.contributor.authorKloos, Arnolden
dc.contributor.authorBoozari, Bitaen
dc.contributor.authorSchache, Peteren
dc.contributor.authorManns, Michael Pen
dc.contributor.authorMalek, Nisar Pen
dc.contributor.authorSparwasser, Timen
dc.contributor.authorZender, Larsen
dc.contributor.authorWirth, Thomas Cen
dc.contributor.authorKubicka, Stefanen
dc.contributor.authorKühnel, Florianen
dc.date.accessioned2012-01-16T14:40:13Z-
dc.date.available2012-01-16T14:40:13Z-
dc.date.issued2011-07-01-
dc.identifier.citationVirus-induced tumor inflammation facilitates effective DC cancer immunotherapy in a Treg-dependent manner in mice. 2011, 121 (7):2570-82 J. Clin. Invest.en
dc.identifier.issn1558-8238-
dc.identifier.pmid21646722-
dc.identifier.doi10.1172/JCI45585-
dc.identifier.urihttp://hdl.handle.net/10033/203309-
dc.description.abstractVaccination using DCs pulsed with tumor lysates or specific tumor-associated peptides has so far yielded limited clinical success for cancer treatment, due mainly to the low immunogenicity of tumor-associated antigens. In this study, we have identified intratumoral virus-induced inflammation as a precondition for effective antitumor DC vaccination in mice. Administration of a tumor-targeted DC vaccine during ongoing virus-induced tumor inflammation, a regimen referred to as oncolysis-assisted DC vaccination (ODC), elicited potent antitumoral CD8+ T cell responses. This potent effect was not replicated by TLR activation outside the context of viral infection. ODC-elicited immune responses mediated marked tumor regression and successful eradication of preestablished lung colonies, an essential prerequisite for potentially treating metastatic cancers. Unexpectedly, depletion of Tregs during ODC did not enhance therapeutic efficacy; rather, it abrogated antitumor cytotoxicity. This phenomenon could be attributed to a compensatory induction of myeloid-derived suppressor cells in Treg-depleted and thus vigorously inflamed tumors, which prevented ODC-mediated immune responses. Consequently, Tregs are not only general suppressors of immune responses, but are essential for the therapeutic success of multimodal and temporally fine-adjusted vaccination strategies. Our results highlight tumor-targeting, replication-competent viruses as attractive tools for eliciting effective antitumor responses upon DC vaccination.en
dc.language.isoenen
dc.subject.meshAnimalsen
dc.subject.meshCancer Vaccinesen
dc.subject.meshCell Lineen
dc.subject.meshDendritic Cellsen
dc.subject.meshHumansen
dc.subject.meshImmunotherapyen
dc.subject.meshMiceen
dc.subject.meshMice, Inbred Strainsen
dc.subject.meshNeoplasmsen
dc.subject.meshNeoplasms, Experimentalen
dc.subject.meshT-Lymphocytes, Regulatoryen
dc.subject.meshVirusesen
dc.titleVirus-induced tumor inflammation facilitates effective DC cancer immunotherapy in a Treg-dependent manner in mice.en
dc.typeArticleen
dc.contributor.departmentDepartment of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.en
dc.identifier.journalThe Journal of clinical investigationen

Related articles on PubMed

This item is licensed under a Creative Commons License
Creative Commons
All Items in HZI are protected by copyright, with all rights reserved, unless otherwise indicated.