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Chronic Lymphocytic Leukemia

Immunomodulatory effects of Toll-like receptor-7 activation on chronic lymphocytic leukemia cells

Leukemia volume 20, pages 286–295 (2006)Cite this article

Abstract

Weak immunogenicity of chronic lymphocytic leukemia (CLL) cells may contribute to disease progression and inhibit effective immunotherapy. Accordingly, agents that enhance the immunogenicity of CLL cells may be useful in immunotherapeutic approaches to this disease. Since Toll-like receptors (TLRs) are major regulators of innate immunity and initiation of adaptive immunity, we studied the effects of viral pathogen associated molecular pattern agonists (that are recognized by TLRs) on the costimulatory phenotype and function of CLL cells. CLL cells (especially those with high endogenous expression of CD38) responded to TLR7-activating imidazoquinolines and guanosine analogs by increasing costimulatory molecule expression, producing inflammatory cytokines, and becoming more sensitive to killing by cytotoxic effectors. Additional activation of protein kinase C pathways increased the ability to stimulate T-cell proliferation, blocked phosphorylation of the transcription factor, signal transducer and activator of transcription (STAT)3, and resulted in the acquisition of a dendritic cell surface phenotype by TLR7-activated CLL cells. Normal B cells also responded to TLR7 activation by increasing costimulatory molecule expression and cytokine production. These findings suggest a potential role for TLR7 agonists in CLL immunotherapy.

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Acknowledgements

Supported by grants from the Leukemia Research Fund of Canada and the Ontario Cancer Research Network (OCRN) (to DS).RM and MT are employed by a company whose (potential) product was studied in this work.

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Author notes

  1. L Radvanyi

    Present address: Department of Melanoma Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, Texas, 77030, USA

Authors and Affiliations

  1. Division of Molecular and Cellular Biology, Research Institute, Sunnybrook and Women's College Health Sciences Center, Toronto, Canada

    D E Spaner, Y Shi, D White, J Mena, C Hammond, J Tomic & J Booth

  2. Toronto-Sunnybrook Regional Cancer Center, Toronto, Canada

    D E Spaner

  3. Department of Medicine, University of Toronto, Toronto, Canada

    D E Spaner

  4. Department of Medical Biophysics, University of Toronto, Toronto, Canada

    D E Spaner, C Hammond & J Tomic

  5. Immunology platform, Sanofi-Pasteur, Toronto, Canada

    L He & L Radvanyi

  6. Department of Pharmacology, 3M Pharmaceuticals, 3M Center, St Paul, MN, USA

    M A Tomai & R L Miller

Authors
  1. D E Spaner
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  2. Y Shi
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  3. D White
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  7. L He
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  8. M A Tomai
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  9. R L Miller
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  10. J Booth
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  11. L Radvanyi
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Corresponding author

Correspondence to D E Spaner.

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Supplementary Information is available on the Leukemia website (http://www.nature.com/leu/).

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Spaner, D., Shi, Y., White, D. et al. Immunomodulatory effects of Toll-like receptor-7 activation on chronic lymphocytic leukemia cells. Leukemia 20, 286–295 (2006). https://doi.org/10.1038/sj.leu.2404061

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  • DOI: https://doi.org/10.1038/sj.leu.2404061

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