[1]黄邵洪,覃 杰,李 昀,等.含表皮生长因子受体的外泌体诱导肿瘤特异性调节T细胞[J].中国药理学通报,2014,(08):1090.
 HUANG Shao-hong,QIN Jie,LI Yun,et al.Epidermal growth factor receptor-containing exosomes induce tumor-specific regulatory T cells[J].Chinese Pharmacological Bulletin,2014,(08):1090.
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含表皮生长因子受体的外泌体诱导肿瘤特异性调节T细胞()
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《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2014年08期
页码:
1090
栏目:
论著
出版日期:
2014-08-15

文章信息/Info

Title:
Epidermal growth factor receptor-containing exosomes induce tumor-specific regulatory T cells
作者:
黄邵洪1覃 杰2李 昀1安 军1张军航1荣 健3
中山大学附属第三医院1.胸心外科、
2.放射科,广东 广州 510630;
3.中山大学附属第一医院麻醉科,广东 广州 510089
Author(s):
HUANG Shao-hong QIN Jie LI Yun AN Jun ZHANG Jun-hang RONG Jian
1. Dept of Cardiothoracic Surgery,
2.Dept of Radiology, the Third Affiliated Hospital, Sun Yet-sen University, Guangzhou 510630, China;
3.Dept of Anesthesiology, the First Affiliated Hospital, Sun Yet-sen University, Guangzhou 510089, China
关键词:
肺癌 表皮生长因子受体 外泌体 树突状细胞 调节T细胞 凋亡
Keywords:
lung cancer epidermal growth factor receptor exosome dendritic cell regulatory T cell apoptosis
分类号:
R329.24;R331.125;R392.11;R392.12;R734.2
文献标志码:
A
摘要:
目的 探讨树突状细胞(DC)能否捕获含表皮生长因子受体(EGFR)外泌体并转化为成熟DC,诱导生成肿瘤特异性调节T细胞,及后者对肿瘤特异性CD8+T细胞的作用。方法 提纯NSCLC肿瘤标本中的外泌体并验证其有EGFR成分,通过外泌体诱导DC转化为免疫耐受型,观察后者诱导生成的调节T细胞对肿瘤特异性CD8+ T细胞的影响。 结果 NSCLC样本中的EGFR阳性率为80%,而对照肺组织仅为2%。与外泌体共培养7 d后,DC呈现IDO表达高于对照组(80.8%±3.2% vs 65.6%±6.4%,P<0.05)。IDO+DC 诱导生成调节T细胞亦明显超过对照组(24.1%±5.2% vs 4.2%±2.3%,P<0.01),进而明显抑制肿瘤特异性CD8+ T细胞增殖(5.4%±0.2% vs 86.7%±9.3%,P<0.01)。结论 肿瘤细胞的EGFR能够通过外泌体形式排出细胞外,EGFR+外泌体能够诱导免疫耐受IDO+DC产生,进而诱导调节T细胞生成,后者对肿瘤特异性CD8+ T细胞有强大抑制作用。
Abstract:
Aim To investigate whether epidermal growth factor receptor(EGFR)-containing exosomes could induce tumor-specific regulatory T cells, and the effects of those T cells on tumor protein-specific CD8+ T cells. Methods The exosomes with EGFR were purified from NSCLC tumor, which modulated tolerogenic property of DCs. Then the induced TolDCs generated tumor-specific Tregs, with which the tumor protein-specific CD8+ T cells were suppressed. Results 80% exosomes were EGFR positive from LC patients while less than 2% exosomes were EGFR positive from control lung tissue. After exposed to the exosomes in the culture for 7 days, the IDO+ DCs proportion was much higher than that in control group(80.8%±3.2% vs 65.6%±6.4%,P<0.05). The induced Tregs was also higher(24.1%±5.2% vs 4.2%±2.3%,P<0.01), which suppressed the proliferation of CD8+ T cells(5.4%±0.2% vs 86.7%±9.3%,P<0.01). Conclusion The purified exosomes induce tolerogenic DCs. Coculture of the tolerogenic DCs and Th0 cells generates the tumor antigen-specific regulatory T cells. The Tregs could suppress the tumor antigen specific CD8+ T cells.

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备注/Memo

备注/Memo:
收稿日期:2014-04-10,修回日期:2014-05-10
基金项目:国家自然科学青年科学基金资助项目(No 81101096); 广东省自然科学基金(No 10451008901005515)
作者简介:黄邵洪(1976-),男,博士,主治医师,研究方向:肺癌及食管肿瘤临床与基础,E-mail:legendhuang@126.com; 荣 健(1971-),女,博士,副教授,副主任医师,研究方向:体外循环及恶性肿瘤临床与基础,通讯作者,E-mail:jiji126@126.com
更新日期/Last Update: 1900-01-01