Journal
NATURE BIOTECHNOLOGY
Volume 22, Issue 12, Pages 1546-1553Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nbt1035
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Funding
- NCI NIH HHS [R01CA90427] Funding Source: Medline
- NIAID NIH HHS [R01AI48480, R01AI48711, T32-AI07495] Funding Source: Medline
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Tumor vaccines represent a promising therapeutic approach, but thus far have achieved only limited success in the clinic. The major challenge is to find a means of overcoming inhibitory immune regulatory mechanisms and eliciting effective T-cell responses to antigens preferentially expressed by tumor cells. Here we show that the stimulatory capacity of dendritic cells (DCs) and the magnitude of adaptive immunity are critically regulated by the suppressor of cytokine signaling (SOCS) 1 in DCs. Silencing SOCS1 in antigen-presenting DCs strongly enhances antigen-specific anti-tumor immunity. Our findings indicate that SOCS1 represents an inhibitory mechanism for qualitatively and quantitatively controlling antigen presentation by DCs and the magnitude of adaptive immunity. This study has implications for understanding the regulation of antigen presentation and for developing more effective tumor vaccines by silencing the critical brake in antigen presentation.
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