TNF-alpha-treated DC exacerbates disease in a murine  tumor metastasis model.
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.
Vohra
Nasreen
N
Department of Translational Science, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
Verhaegen
Monique
M
Martin
Lisa
L
Mackay
Amy
A
Pilon-Thomas
Shari
S
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002469:Cell Separation; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007108:Immune Tolerance; D007167:Immunotherapy / Q000379:methods*; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009362:Neoplasm Metastasis / Q000276:immunology / Q000473:pathology / Q000628:therapy; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10