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

Nature Biotechnology volume 22, pages 1546–1553 (2004)Cite this article

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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Figure 1: SOCS1 negatively regulates the ability of DCs to stimulate antigen-specific CTL in vitro.
Figure 2: SOCS1 negatively regulates DC ability to prime antigen-specific T-cell response in vivo.
Figure 3: In vivo stimulation strongly enhanced CTL responses induced by SOCS1-silenced DCs.
Figure 4: Enhanced anti-tumor immunity induced by SOCS1-silenced DCs.
Figure 5: Enhanced CTL response against a self tumor–associated antigen by SOCS1-silenced DCs.

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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).

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Author notes

  1. Lei Shen and Kevin Evel-Kabler: These authors contributed equally to this work.

Authors and Affiliations

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

    Lei Shen, Randy Strube & Si-Yi Chen

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

    Kevin Evel-Kabler & Si-Yi Chen

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Corresponding author

Correspondence to Si-Yi Chen.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Transfection of DCs by siRNA oligos. (PDF 144 kb)

Supplementary Fig. 2

Q-RT-PCR analysis of SOCS1 levels in oligo-transfected DCs. (PDF 67 kb)

Supplementary Fig. 3

Q-RT-PCR analysis of SOCS1 levels during BM-DC culture. (PDF 40 kb)

Supplementary Fig. 4

Transduction of DCs by LV-SOCS1-siRNA. (PDF 672 kb)

Supplementary Fig. 5

Q-RT-PCR analysis of SOCS1 levels in YFP+ LV-transduced DCs. (PDF 65 kb)

Supplementary Fig. 6

Flow cytometric analysis of CD86. (PDF 163 kb)

Supplementary Fig. 7

Flow cytometric analysis of CD40. (PDF 155 kb)

Supplementary Methods (PDF 13 kb)

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Shen, L., Evel-Kabler, K., Strube, R. et al. Silencing of SOCS1 enhances antigen presentation by dendritic cells and antigen-specific anti-tumor immunity. Nat Biotechnol 22, 1546–1553 (2004). https://doi.org/10.1038/nbt1035

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  • DOI: https://doi.org/10.1038/nbt1035

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