Journal
NATURE MEDICINE
Volume 14, Issue 3, Pages 258-265Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nm1721
Keywords
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Funding
- NCI NIH HHS [R01 CA090427-05, R01 CA090427-03, R01 CA116677-04, R01 CA116677, R01 CA116677-05, R01 CA100841, R01 CA090427, R01 CA090427-02, R01CA90427, R01CA116677, R01 CA090427-04] Funding Source: Medline
- NIAID NIH HHS [R01AI68472, R01 AI068472-04, R01 AI068472, R01 AI068472-05] Funding Source: Medline
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Regulatory T cells (T-reg cells) suppress autoreactive immune responses and limit the efficacy of tumor vaccines; however, it remains a challenge to selectively eliminate or inhibit T-reg cells. In this study, the zinc-finger A20, a negative regulator of the Toll-like receptor and tumor necrosis factor receptor signaling pathways, was found to play a crucial part in controlling the maturation, cytokine production and immunostimulatory potency of dendritic cells (DCs). A20-silenced DCs showed spontaneous and enhanced expression of costimulatory molecules and proinflammatory cytokines and had different effects on T cell subsets: they inhibited T-reg cells and hyperactivated tumor-infiltrating cytotoxic T lymphocytes and T helper cells that produced interleukin-6 and tumor necrosis factor-alpha and were refractory to T-reg cell-mediated suppression. Hence, this study identifies A20 as an antigen presentation attenuator in control of antitumor immune responses during both the priming and the effector phases and provides a strategy to overcome T-reg cell-mediated suppression in an antigen-specific manner, reducing the need to directly target T-reg cells.
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