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肺癌中免疫突触的改变:一种微环境研究方法。

Alteration of the immunological synapse in lung cancer: a microenvironmental approach.

作者信息

Derniame S, Vignaud J-M, Faure G C, Béné M C

机构信息

Laboratoire d'Immunologie, Faculté de Médecine et CHU de Nancy, Vandoeuvre les Nancy, Nancy, France.

出版信息

Clin Exp Immunol. 2008 Oct;154(1):48-55. doi: 10.1111/j.1365-2249.2008.03727.x. Epub 2008 Aug 29.

Abstract

This study was designed to investigate the immunological properties of stroma reaction T cells and tumoral cells by comparison with non-tumoral lung tissue and local lymph nodes in order to explore interactions between tumour cells and the immune system. Immunodetection of major histocompatibility complex (MHC) molecules, CD3/T cell receptor (TCR) complex and T cell subsets markers was carried out in situ on frozen sections, and the semi-quantitative expression of CD3, CD4 and CD8 was examined in flow cytometry on lymphocytes of nodal, tumoral and healthy lung tissue from 62 patients with non-small cell lung cancer. This study showed alterations on lymphocytes and tumour cells in lung cancer, consistent with an impairment of T cell activation. CD3, TCR alpha beta and accessory molecules expression is down-modulated on peri- or intra-tumoral lymphocytes. MHC class I and class II molecules are down-modulated significantly on tumour cells. Other differences were noted, such as the reversed CD4/CD8 ratio of tumour infiltrating cells, compared to healthy lung tissues, consistent with the development of cytotoxic anti-tumoral responses. This study reports on the presence of a strong in vivo immunomodulating effect of tumour cells in human non-small cell lung cancer, likely to impair proper formation of the immunological synapse.

摘要

本研究旨在通过与非肿瘤性肺组织和局部淋巴结进行比较,研究基质反应性T细胞和肿瘤细胞的免疫特性,以探索肿瘤细胞与免疫系统之间的相互作用。在冷冻切片上原位进行主要组织相容性复合体(MHC)分子、CD3/T细胞受体(TCR)复合体和T细胞亚群标志物的免疫检测,并通过流式细胞术检测62例非小细胞肺癌患者的淋巴结、肿瘤组织和健康肺组织淋巴细胞中CD3、CD4和CD8的半定量表达。本研究显示肺癌患者的淋巴细胞和肿瘤细胞存在改变,这与T细胞活化受损一致。肿瘤周围或肿瘤内淋巴细胞上的CD3、TCRαβ和辅助分子表达下调。肿瘤细胞上的MHC I类和II类分子显著下调。还发现了其他差异,例如与健康肺组织相比,肿瘤浸润细胞的CD4/CD8比率倒置,这与细胞毒性抗肿瘤反应的发展一致。本研究报道了人类非小细胞肺癌中肿瘤细胞存在强大的体内免疫调节作用,这可能会损害免疫突触的正常形成。

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