Cytokine expression and dendritic cell density in melanoma sentinel nodes

Cytokine expression and dendritic cell density in melanoma sentinel nodes
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DOI:
10.1097/00008390-200504000-00003
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发表时间:
2005-04-01
期刊:
影响因子:
2.2
通讯作者:
Aliño, S
Aliño, S
中科院分区:
医学4区
文献类型:
--
作者:
Botella-Estrada, R;Dasí, F;Aliño, S

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前哨淋巴结(SLN)是肿瘤所在区域的第一个引流淋巴结。SLN微转移的存在或不存在是黑色素瘤的重要预后因素。由于黑色素瘤的第一传播途径是淋巴,我们知道免疫系统在黑色素瘤反应中起着重要作用,我们假设黑色素瘤及其相应的SLN应构成一个免疫单位。对来自37例接受选择性淋巴结切除术患者的54个SLN的一小部分进行定量逆转录酶-聚合酶链反应(qRT-PCR),以定量以下基因的信使RNA(mRNA)转录物:酪氨酸酶、端粒酶、环氧合酶-1(考克斯-1)、考克斯-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名患者中的11名患者中切除了11个非前哨淋巴结(NSLN),并进行了相同的研究。对10对前哨淋巴结和非前哨淋巴结进行树突状细胞(DCs)免疫组化。与整个组的NSLN相比,SLN中发现考克斯-2、GM-CSF、IFN-γ和IL-10的mRNA表达显著更高。与SLN相比,NSLN中S-100和CD 1a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SLN吸引。然而,某些免疫抑制分子,如IL-10和考克斯-2的存在,可以阻断它们的成熟和它们成为有效抗原呈递者的能力。
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.