The Clinical Significance of CD169-Positive Lymph Node Macrophage in Patients with Breast Cancer

The immune status of patients can impact on the clinical course of cancer. Lymph node (LN) macrophages play critical roles in anti-cancer immunity via the activation of cytotoxic T-lymphocytes (CTLs). In this study, the prognostic significance of CD169+ LN macrophages was examined in patients with breast cancer. For this purpose the number of CD169+ cells and their ratio relative to total macrophages (CD68+) in regional LNs (RLNs), as well as the number of CD8+ CTLs in tumor tissues, were investigated using immunohistochemistry of paraffin-embedded tissue samples from 146 patients with breast cancer. The association of these data with clinicopathological factors was then analyzed. The number of cells positive for the pan-macrophage marker CD68 remained relatively uniform, while the number of CD169+ cells varied across all cases. Moreover, a high density of CD169+ cells correlated with early clinical stage and no LN metastasis, while a higher CD169+ to CD68+ ratio was significantly associated with small tumor size and a low Ki-67+ rate. There was also a significant correlation between the number of CD8+ CTLs and that of CD169+ macrophages in high grade breast cancer cases with a Ki-67 index greater than 40%. However, neither the density nor the ratio of CD169+ cells, nor the density of CD8+ CTLs, were associated with relapse-free survival, distant relapse-free survival, or breast cancer-specific survival. These findings suggest that CD169+ macrophages in RLNs might be a useful marker for assessing clinical stage, including LN states, in patients with breast cancer.

患者的免疫状态可影响癌症的临床病程。淋巴结（Lymph node, LN）巨噬细胞通过激活细胞毒性T淋巴细胞（cytotoxic T-lymphocytes, CTLs），在抗肿瘤免疫中发挥关键作用。本研究旨在评估乳腺癌患者体内CD169阳性LN巨噬细胞的预后价值。为此，我们采用免疫组织化学技术，对146例乳腺癌患者的石蜡包埋组织标本进行检测，分析其区域淋巴结（regional LNs, RLNs）中CD169阳性细胞的数量、其相对于总巨噬细胞（CD68阳性）的比值，以及肿瘤组织内CD8阳性CTLs的数量。随后分析了上述指标与患者临床病理因素的关联。泛巨噬细胞标志物CD68阳性细胞的数量整体相对均一，而CD169阳性细胞的数量在各病例间存在显著差异。此外，CD169阳性细胞的高浸润密度与临床早期分期及无淋巴结转移显著相关；而CD169阳性/CD68阳性的高比值则与肿瘤体积较小及Ki-67阳性率较低显著相关。在Ki-67指数＞40%的高级别乳腺癌病例中，CD8阳性CTLs的数量与CD169阳性巨噬细胞的数量亦存在显著相关性。然而，CD169阳性细胞的浸润密度、占比，以及CD8阳性CTLs的浸润密度，均与无复发生存期、远处无复发生存期及乳腺癌特异性生存期无显著关联。本研究结果提示，区域淋巴结中的CD169阳性巨噬细胞或可作为评估乳腺癌患者临床分期（包括淋巴结状态）的有效生物标志物。