Department of Surgical Oncology and Digestive Surgery, Graduate School of Medical Science, Kagoshima University, Sakuragaoka, Kagoshima, Japan.
J Surg Res. 2011 May 15;167(2):e211-9. doi: 10.1016/j.jss.2009.05.026. Epub 2009 Jun 16.
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.
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.
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.
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.
浸润性肿瘤微环境中的巨噬细胞的功能多样,其作用复杂。本研究旨在研究在胰腺癌中具有 M2 极化功能的肿瘤相关巨噬细胞(TAMs)的作用和预后意义。
从 76 例胰头癌患者中获得福尔马林固定、石蜡包埋的块。所有患者均接受了宏观根治性切除术。我们不仅通过 CD68,还通过 CD163 和 CD204 评估肿瘤侵袭前沿浸润巨噬细胞的数量,CD163 和 CD204 是 M2 极化巨噬细胞的特异性受体。此外,为了评估淋巴管生成,我们通过 D2-40 测量肿瘤侵袭前沿的淋巴管密度。
CD163 或 CD204 阳性巨噬细胞数量较多的病例,淋巴结转移发生率较高。与无淋巴结转移的病例相比,有淋巴结转移的病例淋巴管密度(LVD)显著增加(P=0.0094)。与 CD68 阳性巨噬细胞数量较多的病例相比,LVD 显著增加(P=0.0175)和预后不良(P=0.0171)的病例中,表达 CD163 或 CD204 的巨噬细胞数量较高,但根据 CD68 阳性巨噬细胞的数量没有显著差异。
胰腺癌侵袭前沿的 M2 极化 TAMs 由于加速淋巴转移而与不良预后相关,抑制 M2 极化 TAMs 与肿瘤细胞之间的功能相互作用可能改善预后。