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Exp Cell Res. 2017 Nov 15;360(2):66-73. doi: 10.1016/j.yexcr.2017.07.031. Epub 2017 Aug 4.

Nrf2 suppresses the function of dendritic cells to facilitate the immune escape of glioma cells.

Author information

1
Department of Neurosurgery, The Affiliated Hospital of Hebei University, Baoding, Hebei 071000, China.
2
Department of Neurosurgery, The First Affiliated Hospital of Gannan Medical College, Ganzhou, Jiangxi 341000, China.
3
The Second Department of Cerebral Surgery, Hospital of Traditional Chinese Medicine of Zhangqiu District, Jinan, Shandong 250200, China.
4
Department of Neurosurgery, Binzhou Central Hospital, Binzhou, Shandong 251700,China.
5
Department of Neurosurgery, The Affiliated Xuzhou Hospital of Medical College, Southeast University, Xuzhou, Jiangsu 221009, China. Electronic address: lijundoc@163.com.

Abstract

Nrf2 is presented in dendritic cells (DCs) and contributes to the maintenance of redox homeostasis. However, the expression pattern and function of Nrf2 in the maturation of DCs in the glioma-infiltrated microenvironment remain unrevealed. Our study aims to investigate the roles of Nrf2 in glioma cell-tamed DCs and their impact on the downstream T cell proliferation and cytotoxicity to glioma cells. It was showed that the inducible maturation of DCs was significantly suppressed after stimulation with tumor-conditioned medium (TCM) prepared from glioma cells (LN-18 and U118MG), as suggested by the decreased CD80, CD86 and IL-12 p70 expression and higher levels of IL-10 than the normal astrocyte medium treated DCs. Moreover, the TCM-exposed DCs had significantly increased expression and transcriptional activity of Nrf2 compared to the negative control. Nrf2 inhibition in DC cells substantially antagonized the inhibitory effects of TCM on the maturation and activation of DC cells, reflected by the elevated maturation markers and IL-12 p70. We further confirmed that Nrf2 inhibition in TCM-exposed DC cells promoted the proliferation of T cells as evaluated by the CFSE-labeled assay and Th1 response shown by the elevated production of IFN-γ. The cytotoxic T lymphocyte assay revealed that Nrf2 genetic suppression in DC cells greatly enhanced the capacity of T cells in the cytotoxicity to glioma cells dependent on the E:T ratio. Collectively, our study demonstrated that Nrf2 inhibition in DCs in glioma-exposed microenvironment could enhance the maturation of DCs and the subsequent activation of T cells and their cytotoxicity on glioma cells.

KEYWORDS:

Dendritic cells; Glioma; Immune escape; Nrf2; T cell cytotoxicity

PMID:
28782555
DOI:
10.1016/j.yexcr.2017.07.031
[Indexed for MEDLINE]

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