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

Nature Biotechnology volume 22, pages 15461553 (2004) | Download Citation

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Abstract

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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Acknowledgements

We thank Lisa Rollins, Xiao-Tong Song, Wenhong Ren, Melissa Aldrich, Denise Sanders, Natasha Lapteva and Xue F. Huang for technical assistance and valuable suggestions. This work was supported by grants from the National Institutes of Health (NIH) (R01CA90427, R01AI48480 and R01AI48711), and the Leukemia and Lymphoma Society SCOR award. L.S. was supported by a US Army Prostate Cancer Research Program Postdoctoral fellowship, and K.E. was supported by a predoctoral NIH training grant (T32-AI07495).

Author information

Author notes

    • Lei Shen
    •  & Kevin Evel-Kabler

    These authors contributed equally to this work.

Affiliations

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

    • Lei Shen
    • , Kevin Evel-Kabler
    • , Randy Strube
    •  & Si-Yi Chen
  2. Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.

    • Lei Shen
    • , Randy Strube
    •  & Si-Yi Chen
  3. Department of Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.

    • Kevin Evel-Kabler
    •  & Si-Yi Chen

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Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Si-Yi Chen.

Supplementary information

PDF files

  1. 1.

    Supplementary Fig. 1

    Transfection of DCs by siRNA oligos.

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    Supplementary Fig. 2

    Q-RT-PCR analysis of SOCS1 levels in oligo-transfected DCs.

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    Supplementary Fig. 3

    Q-RT-PCR analysis of SOCS1 levels during BM-DC culture.

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    Supplementary Fig. 4

    Transduction of DCs by LV-SOCS1-siRNA.

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    Supplementary Fig. 5

    Q-RT-PCR analysis of SOCS1 levels in YFP+ LV-transduced DCs.

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    Supplementary Fig. 6

    Flow cytometric analysis of CD86.

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    Supplementary Fig. 7

    Flow cytometric analysis of CD40.

  8. 8.

    Supplementary Methods

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DOI

https://doi.org/10.1038/nbt1035

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