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黑色素瘤前哨淋巴结中的细胞因子表达及树突状细胞密度

Cytokine expression and dendritic cell density in melanoma sentinel nodes.

作者信息

Botella-Estrada Rafael, Dasí Francisco, Ramos David, Nagore Eduardo, Herrero Maria Jose, Giménez Julia, Fuster Carlos, Sanmartín Onofre, Guillén Carlos, Aliño Salvador

机构信息

Department of Dermatology, Instituto Valenciano de Oncología, Valencia, Spain.

出版信息

Melanoma Res. 2005 Apr;15(2):99-106. doi: 10.1097/00008390-200504000-00003.

DOI:10.1097/00008390-200504000-00003
PMID:15846142
Abstract

The sentinel lymph node (SLN) is the first draining node from the area in which a tumour is located. The presence or absence of SLN micrometastasis is an important prognostic factor for melanoma. As the first dissemination route for melanoma is lymphatic and we know that the immune system plays an important role in melanoma response, we hypothesize that melanoma and its corresponding SLN should constitute an immunological unit. Small portions of 54 SLNs from 37 patients undergoing selective lymphadenectomy were subjected to quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) to quantify messenger RNA (mRNA) transcripts of the following genes: tyrosinase, telomerase, cyclooxygenase-1 (COX-1), COX-2, granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), interferon-gamma (IFN-gamma), IL-4, IL-10 and IL-12. In addition, 11 non-sentinel lymph nodes (NSLNs) were excised from 11 of the 37 patients and the same study was performed. Immunohistochemistry with different antibodies against dendritic cells (DCs) was performed in 10 pairs of SLNs and NSLNs. Significantly higher mRNA expression of COX-2, GM-CSF, IFN-gamma and IL-10 was found in SLNs compared with NSLNs in the overall group. DCs, as labelled by S-100 and CD1a, were significantly decreased in NSLNs compared with SLNs. These data suggest that the initial increase in GM-CSF observed in SLNs could lead to the attraction of a high number of DCs to SLNs. However, the presence of certain immunosuppressive molecules, such as IL-10 and COX-2, could block their maturation and their ability to become efficient antigen presenters.

摘要

前哨淋巴结(SLN)是肿瘤所在区域的首个引流淋巴结。SLN微转移的有无是黑色素瘤的一个重要预后因素。由于黑色素瘤的首个播散途径是淋巴途径,且我们知道免疫系统在黑色素瘤反应中起重要作用,因此我们推测黑色素瘤及其相应的SLN应构成一个免疫单位。对37例行选择性淋巴结清扫术患者的54个SLN的小部分组织进行定量逆转录聚合酶链反应(qRT-PCR),以定量以下基因的信使核糖核酸(mRNA)转录本:酪氨酸酶、端粒酶、环氧化酶-1(COX-1)、COX-2、粒细胞-巨噬细胞集落刺激因子(GM-CSF)、白细胞介素-2(IL-2)、干扰素-γ(IFN-γ)、IL-4、IL-10和IL-12。此外,从37例患者中的11例切除了11个非前哨淋巴结(NSLN),并进行了相同的研究。对10对SLN和NSLN进行了针对树突状细胞(DC)的不同抗体的免疫组织化学检测。在总体组中,与NSLN相比,SLN中COX-2、GM-CSF、IFN-γ和IL-10的mRNA表达显著更高。与SLN相比,NSLN中由S-100和CD1a标记的DC显著减少。这些数据表明,在SLN中观察到的GM-CSF的初始增加可能导致大量DC被吸引至SLN。然而,某些免疫抑制分子如IL-10和COX-2的存在可能会阻止它们的成熟及其成为高效抗原呈递细胞的能力。

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