Significance of M2-Polarized Tumor-Associated Macrophage in Pancreatic Cancer

Significance of M2-Polarized Tumor-Associated Macrophage in Pancreatic Cancer
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DOI:
10.1016/j.jss.2009.05.026
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发表时间:
2011-05-01
影响因子:
2.2
通讯作者:
Takao, Sonshin
Takao, Sonshin
中科院分区:
医学3区
文献类型:
--
作者:
Kurahara, Hiroshi;Shinchi, Hiroyuki;Takao, Sonshin

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背景浸润性巨噬细胞在肿瘤微环境中的作用是复杂的,因为它们的功能多样性。本研究的目的是研究胰腺癌中具有M2极化功能的肿瘤相关巨噬细胞(TAMs)的作用和预后意义。福尔马林固定,石蜡包埋块从76例胰头癌患者。所有患者均行肉眼根治性切除。我们不仅通过CD 68,而且通过CD 163和CD 204(M2极化巨噬细胞上的特异性受体)评估了肿瘤浸润前沿内浸润巨噬细胞的数量。采用D2- 40法测量肿瘤浸润前沿淋巴管密度,评价淋巴管生成情况。在CD 163或CD 204阳性巨噬细胞数量较多的病例中,淋巴结转移的发生率较高。淋巴结转移组淋巴管密度(LVD)明显高于无淋巴结转移组(P = 0.0094)。在表达CD 163或CD 204的巨噬细胞数量高的病例中,LVD显著增加(P = 0.0175),预后差(P = 0.0171),但根据CD 68阳性的巨噬细胞数量,LVD无显著差异。胰腺癌侵袭性前沿的M2极化TAM由于加速淋巴转移而与不良预后相关,抑制M2极化TAM与肿瘤细胞之间的功能相互作用可改善预后。(C)2011 Elsevier Inc. All rights reserved.
Background. The roles of infiltrating macrophages within the tumor microenvironment are complex because of their functional variety. The aim of this study is to examine the role and prognostic significance of tumor-associated macrophages (TAMs) that have an M2 polarized function in pancreatic cancer.Materials and Methods. Formalin-fixed, paraffin-embedded blocks were obtained from 76 patients with pancreatic head cancer. All patients underwent macroscopic curative resection. We assessed the number of infiltrating macrophages within the tumor invasive front by not only CD68 but also by CD163 and CD204, which are specific receptors on M2-polarized macrophages. Furthermore, to evaluate lymphangiogenesis, we measured the density of lymphatic vessels in the tumor invasive front by using D2-40.Results. High incidence of lymph node metastasis was shown in cases with a high number of CD163- or CD204-positive macrophages. Significantly increased lymphatic vessel density (LVD) was shown in cases with lymph node metastasis compared with cases without lymph node metastasis (P = 0.0094). Significantly increased LVD (P = 0.0175) and a poor prognosis (P = 0.0171) were shown in cases with a high number of macrophages that express CD163 or CD204, however, there was no significant difference according to the number of CD68-positive macrophages.Conclusions. M2-polarized TAMs in the invasive front of pancreatic cancer are associated with a poor prognosis due to accelerated lymphatic metastasis, and inhibition of the functional interaction between M2-polarized TAMs and tumor cells may improve the prognosis. (C) 2011 Elsevier Inc. All rights reserved.