Title |
Transient Foxp3+ regulatory T‐cell depletion enhances therapeutic anticancer vaccination targeting the immune‐stimulatory properties of NKT cells
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Published in |
Immunology & Cell Biology, October 2012
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DOI | 10.1038/icb.2012.58 |
Pubmed ID | |
Authors |
Stephen R Mattarollo, Kim Steegh, Ming Li, Helene Duret, Shin Foong Ngiow, Mark J Smyth |
Abstract |
The natural killer T (NKT) cell ligand, alpha-galactosylceramide (α-GalCer), represents a potential adjuvant to boost immunotherapeutic vaccination strategies against poorly immunogenic cancers. The objective of this study was to assess the therapeutic potential of an α-GalCer-loaded tumor-cell vaccine against solid tumors in mice and to enhance the effectiveness of this approach by removing immune suppression associated with the activity of Foxp3(+) regulatory T cells (Tregs). In the B16F10 melanoma model, we show that single vaccination with irradiated, α-GalCer-loaded tumor cells resulted in suppression of established subcutaneous (s.c.) B16F10 tumor growth, which was mediated by NKT cell-dependent IFN-γ production and enhanced in the absence of IL-17 A. Selective depletion of Foxp3(+) Tregs in transgenic DEpletion of REGulatory T cells (DEREG) mice led to significant inhibition of B16F10 tumor growth and enhanced survival of mice receiving vaccination. Short-term elimination of Foxp3(+) Tregs (<7 days) was sufficient to boost vaccine-induced immunity. Enhanced antitumor activity with combination therapy was associated with an increase in systemic NK cell and effector CD8(+) T-cell activation and IFN-γ production, as well as infiltration of effector CD8(+) T cells into the tumor. Overall, these findings demonstrate that transient depletion of Foxp3(+) Tregs constitutes a highly effective strategy to improve the therapeutic efficacy of anticancer vaccination with NKT cell adjuvants. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Germany | 1 | 2% |
Switzerland | 1 | 2% |
Israel | 1 | 2% |
India | 1 | 2% |
United Kingdom | 1 | 2% |
United States | 1 | 2% |
Unknown | 53 | 90% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 14 | 24% |
Researcher | 14 | 24% |
Student > Postgraduate | 6 | 10% |
Other | 4 | 7% |
Professor > Associate Professor | 4 | 7% |
Other | 7 | 12% |
Unknown | 10 | 17% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 20 | 34% |
Medicine and Dentistry | 9 | 15% |
Immunology and Microbiology | 7 | 12% |
Biochemistry, Genetics and Molecular Biology | 6 | 10% |
Engineering | 2 | 3% |
Other | 5 | 8% |
Unknown | 10 | 17% |