TNF-alpha-treated DC exacerbates disease in a murine tumor metastasis model
- 17 November 2009
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cancer Immunology, Immunotherapy
- Vol. 59 (5), 729-736
- https://doi.org/10.1007/s00262-009-0793-5
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.Keywords
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