曹雪涛院士连发4篇文章解析癌症机制

【字体: 时间:2009年06月05日 来源:生物通

编辑推荐:

  生物通报道,第二军医大国家重点医学免疫和免疫学实验室,浙江大学医学院免疫研究所的科研人员在最近一期的《The Journal of Immunology》上发表肿瘤抗药机制新进展,Tumor-Educated CD11bhighIalow Regulatory Dendritic Cells Suppress T Cell Response through Arginase I1,通讯作者为曹雪涛院士。

  

生物通报道,第二军医大国家重点医学免疫和免疫学实验室,浙江大学医学院免疫研究所的科研人员在最近一期的《The Journal of Immunology》上发表肿瘤抗药机制新进展,Tumor-Educated CD11bhighIalow Regulatory Dendritic Cells Suppress T Cell Response through Arginase I1,通讯作者为曹雪涛院士。

 

2009年,加上本篇论文,曹雪涛院士在《The Journal of Immunology》发表了4篇文章。分别解析肿瘤免疫逃避机制,分泌载体膜蛋白研究进展以及癌症与炎症的关系。(详细内容参见生物通前期报道:http://www.ebiotrade.com/newsf/2009-1/2009119163720.htm  http://www.ebiotrade.com/newsf/2009-3/2009317171017.htm  http://www.ebiotrade.com/newsf/2009-3/2009330172538.htm

 

世纪杀手癌症具有复杂的逃避免疫攻击的机制,其中一种伎俩就是在肿瘤微环境中不断诱导产生抑制免疫的调节性T细胞蓄积,协助癌细胞逃避免疫攻击。尽管目前以树突细胞(dendritic cellDC)为基础的癌症疫苗可以诱发自动的抗肿瘤免疫,但是人们逐渐发现调节性DC细胞亚群可能诱导肿瘤抗药性,这一研究领域逐步受到重视。

 

曹雪涛小组发现在脾、肺和肝的间质微环境中,具有调节功能的树突细胞逐步产生(CD11clowCD11bhighIalow DCs)。这类树突细胞的产生会促进肿瘤细胞逃避免疫攻击,然而,在肿瘤微环境中,这类细胞是如何产生的,机制一直不明朗。

 

在本研究者,曹雪涛等人从肿瘤组织中分离新鲜的肿瘤细胞模拟肿瘤微环境,在这个环境中培养树突细胞,结果发现肿瘤细胞能促进树突细胞分化成各种不同功能的树突细胞亚类,包括调节性的树突细胞亚类。

 

最后,研究结果证实肿瘤细胞能促进树突细胞分化成诱导肿瘤抗药的调节性树突细胞亚类。

(生物通 小茜)

 

生物通推荐原文检索:Tumor-Educated CD11bhighIalow Regulatory Dendritic Cells Suppress T Cell Response through Arginase I1

 

Qiuyan Liu*, Chaoxiong Zhang*, Anna Sun, Yuanyuan Zheng*, Li Wang and Xuetao Cao2,*,

* National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai, People’s Republic of China; and  Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China

Abstract

Tumors can induce generation and accumulation of the immunosuppressive cells such as regulatory T cells in the tumor microenvironment, contributing to tumor escape from immunological attack. Although dendritic cell (DC)-based cancer vaccine can initiate antitumor immune response, regulatory DC subsets involved in the tolerance induction attracted much attention recently. Our previous studies demonstrate that the stromal microenvironment of the spleen, lung, and liver can program generation of CD11clowCD11bhighIalow DCs with regulatory function (CD11bhighIalow regulatory DCs). However, whether and how the tumor microenvironment can program generation of CD11bhighIalow regulatory DCs remain to be investigated. In this study, we used the freshly isolated tumor cells to mimic tumor microenvironment to coculture DCs and found that the freshly isolated tumor cells could drive DCs to differentiate into regulatory DCs with a CD11clowCD11bhighIalow phenotype and high expression of IL-10, NO, vascular endothelial growth factor, and arginase I. Tumor-educated CD11bhighIalow regulatory DCs inhibited CD4+ T cell proliferation both in vitro and in vivo. 3LL lung cancer-derived TGF-β and PGE2 were responsible for the generation of regulatory DCs. PGE2 was the main inducer of arginase I in regulatory DCs. Arginase I played a major role in the suppression of T cell response by regulatory DCs induced by 3LL lung cancer. A natural counterpart of CD11bhighIalow DCs was identified in tumor tissue, and CD11bhighIalow DCs sorted from 3LL lung cancer tissue expressed arginase I and inhibited T cell response. Therefore, tumors can educate DCs to differentiate into a regulatory DC subset, which contributes to constitution of the immunosuppressive tumor microenvironment and promotes tumor immune escape.

 

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

 

1 This work was supported by grants from the National Natural Science Foundation of China (Grants 30771984, 30672386, and 30721091) and the National Key Research Program of China (Grant 2007CB512403).

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