Virus-induced tumor inflammation facilitates effective DC cancer immunotherapy in a Treg-dependent manner in mice.
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Authors
Woller, NormanKnocke, 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
Issue Date
2011-07-01
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Show full item recordAbstract
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.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.Affiliation
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.DOI
10.1172/JCI45585PubMed ID
21646722Type
ArticleLanguage
enISSN
1558-8238ae974a485f413a2113503eed53cd6c53
10.1172/JCI45585
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