Article abstract
Nature Medicine 14, 258 - 265 (2008)
Published online: 2 March 2008 | doi:10.1038/nm1721
A20 is an antigen presentation attenuator, and its inhibition overcomes regulatory T cell–mediated suppression
Xiao-Tong Song1,3, Kevin Evel Kabler1,3, Lei Shen1, Lisa Rollins1, Xue F Huang1,2 & Si-Yi Chen1,2
Abstract
Regulatory T cells (Treg cells) suppress autoreactive immune responses and limit the efficacy of tumor vaccines; however, it remains a challenge to selectively eliminate or inhibit Treg 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 Treg cells and hyperactivated tumor-infiltrating cytotoxic T lymphocytes and T helper cells that produced interleukin-6 and tumor necrosis factor-
and were refractory to Treg 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 Treg cell–mediated suppression in an antigen-specific manner, reducing the need to directly target Treg cells.
- Center for Cell and Gene Therapy, Baylor College of Medicine (BCM), One Baylor Plaza, Houston, Texas 77030, USA.
- Department of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California (USC), 1450 Biggy Street, Los Angeles, California 90033, USA.
- These authors contributed equally to this study.
Correspondence to: Si-Yi Chen1,2 e-mail: siyichen@usc.edu
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