Dexamethasone enhances programmed cell death 1 (PD-1) expression during T cell activation: an insight into the optimum application of glucocorticoids in anti-cancer therapy.
Dexamethasone enhances programmed cell death 1 (PD-1) expression during T cell activation: an insight into the optimum application of glucocorticoids in anti-cancer therapy.
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地塞米松增强 T 细胞激活过程中程序性细胞死亡 1 (PD-1) 的表达：深入了解糖皮质激素在抗癌治疗中的最佳应用
DOI：
10.1186/s12865-015-0103-2
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发表时间：
2015-06-26
期刊：
影响因子：
3
通讯作者：
Wu X
中科院分区：
文献类型：
--
作者：
Xing K;Gu B;Zhang P;Wu X
研究背景程序性细胞死亡1（PD-1）是CD 28超家族的一个重要的细胞表面受体，它通过触发抑制性通路来减弱T细胞反应和促进T细胞耐受。PD-1在肿瘤免疫中起着重要作用，已成为抗肿瘤治疗研究的热点。已经证实，肿瘤可以利用PD-1依赖性免疫抑制进行免疫逃避。鉴于糖皮质激素（glucocorticoids，GCs）在抗肿瘤治疗中的广泛应用及其免疫抑制作用，本研究探讨GCs对PD-1表达的影响。结果以地塞米松（dexamethasone，DEX）为模型糖皮质激素，DEX可促进PD-1的表达，且呈剂量依赖性。糖皮质激素受体（GR）拮抗剂米非司酮（RU 486）完全抑制了这种作用，表明DEX对PD-1的作用是通过GR介导的。我们进一步发现，不同T细胞亚群对DEX诱导的PD-1表达上调的敏感性存在显著差异，记忆T细胞更容易受到这种作用的影响。结论DEX可通过抑制T细胞产生IL-2、IFN-γ、TNF-α等细胞因子，诱导T细胞凋亡，从而抑制T细胞功能。
BackgroundProgrammed cell death 1 (PD-1) is a key cell-surface receptor of CD28 superfamily that triggers inhibitory pathways to attenuate T-cell responses and promote T-cell tolerance. As a crucial role in tumor immunity, PD-1 has been a focus of studies in anti-cancer therapy. It has been approved that tumors could exploit PD-1-dependent immune suppression for immune evasion. Considering the wide use of glucocorticoids (GCs) in anti-cancer therapy and their immunosuppressive effects, we explored whether GCs could influence the expression of PD-1.ResultsIn our study, we used dexamethasone (DEX) as a model glucocorticoid and demonstrated that DEX could enhance PD-1 expression in a dose-dependent manner. The effects were completely inhibited by the glucocorticoid receptor (GR) antagonist mifepristone (RU486), indicating that the effect of DEX on PD-1 is mediated through GR. We further found the sensitivity to DEX-induced upregulation of PD-1 expression had a significant difference between different T cell subsets, with memory T cells more susceptible to this effect. We also showed that DEX could suppress T cell functions via inhibition of cytokines production such as IL-2, IFN-γ, TNF-α and induction of apoptosis of T cells.ConclusionOur findings suggest a novel way by which DEX suppress the function of activated T lymphocytes by enhancing expression of PD-1 and provide an insight into the optimum clinical application of GCs.
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影响因子：
4.4
作者：
Chemnitz, JM;Parry, RV;Riley, JL
通讯作者：
Riley, JL
DOI：
10.1196/annals.1321.009
发表时间：
2004-01-01
期刊：
GLUCOCORTICOID ACTION: BASIC AND CLINICAL IMPLICATIONS
影响因子：
--
作者：
Franchimont, D
通讯作者：
Franchimont, D
DOI：
10.1073/pnas.0406351101
发表时间：
2004-12-07
影响因子：
11.1
作者：
Thompson, RH;Gillettt, MD;Kwon, ED
通讯作者：
Kwon, ED
影响因子：
3.4
作者：
Chiou, SH;Sheu, BC;Ho, HN
通讯作者：
Ho, HN
影响因子：
8
作者：
Xia, M;Gasser, J;Feige, U
通讯作者：
Feige, U