Journal
CANCER IMMUNOLOGY IMMUNOTHERAPY
Volume 56, Issue 1, Pages 48-59Publisher
SPRINGER
DOI: 10.1007/s00262-006-0160-8
Keywords
tumor immunity; tolerance; dendritic cells; regulatory T cells
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Funding
- NCI NIH HHS [R01 CA104926] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [R01CA104926] Funding Source: NIH RePORTER
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CD4(+) CD25(+) regulatory T cells have been characterized as a critical population of immunosuppressive cells. They play a crucial role in cancer progression by inhibiting the effector function of CD4(+) or CD8(+) T lymphocytes. However, whether regulatory T lymphocytes that expand during tumor progression can modulate dendritic cell function is unclear. To address this issue, we have evaluated the inhibitory potential of CD4(+) CD25(+) regulatory T cells from mice bearing a BCR-ABL(+) leukemia on bone marrow-derived dendritic cells. We present data demonstrating that CD4(+) CD25(+) FoxP3(+) regulatory T cells from tumor-bearing animals impede dendritic cell function by downregulating the activation of the transcription factor NF-kappa B. The expression of the co-stimulatory molecules CD80, CD86 and CD40, the production of TNF-alpha, IL-12, and CCL5/RANTES by the suppressed DC is strongly down-regulated. The suppression mechanism requires TGF-beta and IL-10 and is associated with induction of the Smad signaling pathway and activation of the STAT3 transcription factor.
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