Sandel Maro H, Dadabayev Alisher R, Menon Anand G, Morreau Hans, Melief Cornelis J M, Offringa Rienk, van der Burg Sjoerd H, Janssen-van Rhijn Connie M, Ensink N Geeske, Tollenaar Rob A E M, van de Velde Cornelis J H, Kuppen Peter J K
Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands.
Clin Cancer Res. 2005 Apr 1;11(7):2576-82. doi: 10.1158/1078-0432.CCR-04-1448.
The clinical significance of tumor-infiltrating dendritic cells has been reported in a variety of human solid tumors as shown by the correlations found between the presence of tumor-infiltrating dendritic cells and clinical prognosis. In this study, we evaluated whether there is an association between the presence and maturation status of tumor-infiltrating dendritic cells, T lymphocytes, and clinical course in 104 primary tumor samples of patients with colorectal cancer. Dendritic cells were identified with four different markers (S-100, HLA class II, CD208, and CD1a) in double immunohistochemistry, with laminin as second marker to support the exact localization. Tumor-infiltrating dendritic cells showed a distinct infiltration pattern based on their maturation status. CD1a-positive dendritic cells resided in the advancing tumor margins in relatively high numbers, whereas mature CD208-positive dendritic cells were sparsely present in the tumor epithelium but mainly distributed in the tumor stroma and advancing tumor margin. Furthermore, high infiltration of CD1a-positive dendritic cells in the tumor epithelium was significantly correlated to the infiltration of CD4 lymphocytes (P = 0.006). Patients with relatively high numbers of mature CD208-positive infiltrating dendritic cells in the tumor epithelium had a shorter overall survival (P = 0.004). In addition, patients with relatively high numbers of CD1a-positive dendritic cells in the advancing margin of the tumor had a shorter disease-free survival (P = 0.03). We found that tumor-infiltrating dendritic cells had preferential infiltration sites within a tumor, affected local tumor cell-immune cell interactions, and correlated to the clinical prognosis of colorectal cancer patients.
肿瘤浸润性树突状细胞的临床意义已在多种人类实体瘤中得到报道，肿瘤浸润性树突状细胞的存在与临床预后之间的相关性就表明了这一点。在本研究中，我们评估了104例结直肠癌患者的原发性肿瘤样本中肿瘤浸润性树突状细胞、T淋巴细胞的存在及成熟状态与临床病程之间是否存在关联。在双重免疫组织化学中，用四种不同的标志物（S-100、HLA II类分子、CD208和CD1a）鉴定树突状细胞，用层粘连蛋白作为第二种标志物以支持精确定位。肿瘤浸润性树突状细胞根据其成熟状态呈现出不同的浸润模式。CD1a阳性树突状细胞大量存在于肿瘤进展边缘，而成熟的CD208阳性树突状细胞在肿瘤上皮中稀疏存在，但主要分布在肿瘤基质和肿瘤进展边缘。此外，肿瘤上皮中CD1a阳性树突状细胞的高浸润与CD4淋巴细胞的浸润显著相关（P = 0.006）。肿瘤上皮中成熟的CD208阳性浸润性树突状细胞数量相对较多的患者总生存期较短（P = 0.004）。此外，肿瘤进展边缘CD1a阳性树突状细胞数量相对较多的患者无病生存期较短（P = 0.03）。我们发现肿瘤浸润性树突状细胞在肿瘤内有优先浸润部位，影响局部肿瘤细胞与免疫细胞的相互作用，并与结直肠癌患者的临床预后相关。
