Tumor-derived CD4+CD25+ regulatory T cell suppression of dendritic cell function involves TGF-β and IL-10

Nicolas Larmonier, Marilyn Marron, Yi Zeng, Jessica Cantrell, Angela Romanoski, Marjan Sepassi, Sylvia Thompson, Xinchun Chen, Samita Andreansky, Emmanuel Katsanis

Research output: Contribution to journalArticlepeer-review

156 Scopus citations

Abstract

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 down-regulating the activation of the transcription factor NF-κB. The expression of the co-stimulatory molecules CD80, CD86 and CD40, the production of TNF-α, IL-12, and CCL5/RANTES by the suppressed DC is strongly down-regulated. The suppression mechanism requires TGF-β and IL-10 and is associated with induction of the Smad signaling pathway and activation of the STAT3 transcription factor.

Original languageEnglish (US)
Pages (from-to)48-59
Number of pages12
JournalCancer Immunology, Immunotherapy
Volume56
Issue number1
DOIs
StatePublished - Jan 1 2007

Keywords

  • Dendritic cells
  • Regulatory T cells
  • Tolerance
  • Tumor immunity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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