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TNF-alpha-treated DC exacerbates disease in a murine tumor metastasis model

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Abstract

Due to the pivotal role that dendritic cells (DC) play in eliciting functional anti-tumor T cell responses, immunotherapeutic approaches utilizing DC-based vaccines have readily been exploited. It has been argued that, in the setting of immunotherapy, mature DC will be more efficient at T cell priming and, therefore, required for effective vaccination. As TNF-alpha is commonly used as a DC maturation factor, we have examined the efficacy of treatment with DC matured with TNF-alpha (DC-TNF) in a murine model of melanoma. We have now shown that treatment with DC-TNF leads to an increase in the number of lung metastases as compared to mice treated with immature DC. No differences in the number of CD4+CD25+ T-regulatory cells were measured in the lungs of DC-TNF-treated mice. On examination of the infiltrating lymphocytes, an enhanced secretion of IL-10 and a higher percentage of CD4+IL-10+ T cells were measured in the lungs of DC-TNF-treated mice. However, treatment with DC-TNF did not enhance the number of melanoma lesions in the lungs of IL-10 knockout mice or in mice depleted of CD4+ T cells. Together, these studies indicate that treatment of melanoma-bearing mice with DC treated with TNF-alpha can induce IL-10 production by resident cells at the tumor site, leading to immune tolerance and exacerbation of disease.

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Acknowledgments

This work was supported by the National Cancer Institute Grant K99CA128825-01 (SPT). We thank the Ocala Royal Dames for Cancer Research for their generous support. We thank the Flow Cytometry Core Facility at the H. Lee Moffitt Cancer Center and Research Institute for its contribution to this work.

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Authors and Affiliations

  1. Department of Translational Science, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr, SRB-3, Tampa, FL, 33612, USA

    Nasreen Vohra, Lisa Martin, Amy Mackay & Shari Pilon-Thomas

  2. Department of Surgery, University of South Florida, Tampa, FL, USA

    Nasreen Vohra

  3. Department of Dermatology, University of Michigan, Ann Arbor, MI, USA

    Monique Verhaegen

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  1. Nasreen Vohra
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  2. Monique Verhaegen
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Correspondence to Shari Pilon-Thomas.

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Vohra, N., Verhaegen, M., Martin, L. et al. TNF-alpha-treated DC exacerbates disease in a murine tumor metastasis model. Cancer Immunol Immunother 59, 729–736 (2010). https://doi.org/10.1007/s00262-009-0793-5

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  • DOI: https://doi.org/10.1007/s00262-009-0793-5

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