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Article
Nature Biotechnology  22, 1546 - 1553 (2004)
Published online: 21 November 2004; | doi:10.1038/nbt1035

Silencing of SOCS1 enhances antigen presentation by dendritic cells and antigen-specific anti-tumor immunity

Lei Shen1, 2, 4, Kevin Evel-Kabler1, 3, 4, Randy Strube1, 2 & Si-Yi Chen1, 2, 3

1  Center for Cell and Gene Therapy, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.

2  Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.

3  Department of Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.

4  These authors contributed equally to this work.

Correspondence should be addressed to Si-Yi Chen sychen@bcm.tmc.edu
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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Nature Biotechnology
ISSN: 1087-0156
EISSN: 1546-1696
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