Department of Molecular Diagnostic Pathology, Iwate Medical University, Yahaba-cho, Japan.
Department of Thoracic Surgery, Iwate Medical University, Yahaba-cho, Japan.
Thorac Cancer. 2023 Jul;14(20):1911-1920. doi: 10.1111/1759-7714.14937. Epub 2023 May 20.
Macrophages infiltrating the tumor microenvironment are defined as tumor-associated macrophages (TAMs). TAMs can be polarized into different phenotypes, that is, proinflammatory M1 macrophages or anti-inflammatory M2 macrophages. Particularly, M2 macrophages promote angiogenesis, wound healing, and tumor growth. This study aimed to evaluate whether M2 TAMs can serve as a useful marker to predict prognosis and benefit from adjuvant chemotherapy in patients with surgically resected lung squamous cell carcinomas (SCCs).
We examined 104 patients with SCC. Tissue microarrays were constructed, and the density of TAMs was analyzed by immunohistochemistry for expression of CD68 and CD163. The relationship between CD68 and CD163 expression and the CD163/CD68 expression rate and clinicopathological characteristics including patient outcomes were investigated. In addition, propensity score matching (PSM) analysis was conducted to test the hypothesis that these cells significantly influenced chemotherapy responses.
Univariate analysis revealed that pathological stage, CD163 expression, and the CD163/CD68 expression ratio were significant prognostic factors. Multivariate analysis showed that these factors were all independent prognostic factors. Thirty-four pairs were determined by using PSM analysis. Patients with a low CD163/CD68 expression ratio benefited more from adjuvant chemotherapy than those with a high ratio.
We suggest that M2 TAMs may be a useful marker to predict prognosis and differential benefit from adjuvant chemotherapy in patients with surgically resected lung SCCs.
浸润肿瘤微环境的巨噬细胞被定义为肿瘤相关巨噬细胞(TAMs)。TAMs 可以极化为不同的表型,即促炎 M1 巨噬细胞或抗炎 M2 巨噬细胞。特别是 M2 巨噬细胞促进血管生成、伤口愈合和肿瘤生长。本研究旨在评估 M2 TAMs 是否可以作为预测手术切除的肺鳞状细胞癌(SCC)患者预后和从辅助化疗中获益的有用标志物。
我们检查了 104 例 SCC 患者。构建组织微阵列,通过免疫组织化学分析 CD68 和 CD163 的表达来分析 TAMs 的密度。研究了 CD68 和 CD163 表达之间的关系,以及 CD163/CD68 表达率与包括患者结局在内的临床病理特征之间的关系。此外,进行倾向评分匹配(PSM)分析以检验这些细胞显著影响化疗反应的假设。
单因素分析显示,病理分期、CD163 表达和 CD163/CD68 表达比是显著的预后因素。多因素分析显示,这些因素都是独立的预后因素。通过 PSM 分析确定了 34 对。CD163/CD68 表达比值低的患者从辅助化疗中获益更多,而比值高的患者获益较少。
我们认为 M2 TAMs 可能是预测手术切除的肺 SCC 患者预后和从辅助化疗中获益差异的有用标志物。