Macrophage and mast-cell invasion of tumor cell islets confers a marked survival advantage in non-small-cell lung cancer
Macrophage and mast-cell invasion of tumor cell islets confers a marked survival advantage in non-small-cell lung cancer
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DOI：
10.1200/jco.2005.01.4910
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发表时间：
2005-12-10
影响因子：
45.3
通讯作者：
Bradding, P
中科院分区：
文献类型：
--
作者：
Welsh, TJ;Green, RH;Bradding, P
目的先天免疫系统在决定非小细胞肺癌（NSCLC）患者生存率方面的作用尚不清楚。方法采用免疫组织化学方法检测175例NSCLC患者肿瘤间质和肿瘤胰岛中类胰蛋白酶阳性肥大细胞和CD 68阳性巨噬细胞的表达，并分析其与预后的关系。肥大细胞分别在99.4%和68.5%的患者的间质和胰岛中检测到。采用多变量考克斯比例风险分析，增加肿瘤胰岛巨噬细胞密度（P <0.001）和肿瘤胰岛/间质巨噬细胞比率（P <0.001）是有利的独立预后指标。相反，基质巨噬细胞密度增加是生存率降低的独立预测因子（P = 0.001）。肿瘤胰岛肥大细胞的存在（P = 0.018）和胰岛/间质肥大细胞比率的增加（P = 0.032）也是有利的独立预后指标。巨噬细胞胰岛密度显示出最强的影响：胰岛巨噬细胞密度大于中位数的患者5年生存率为52.9%，小于中位数的患者为7%（P <0.0001）。在同一组中，中位生存期分别为2,244天和334天（P < .0001）。结论肿瘤胰岛CD 68（+）巨噬细胞密度是NSCLC手术切除后生存的独立预测因子。对此的生物学解释及其对连续治疗的影响需要进一步研究。
Purpose The role played by the innate immune system in determining survival from non-small-cell lung cancer (NSCLC) is unclear. The aim of this study was to investigate the prognostic significance of macrophage and mast-cell infiltration in NSCLC.Methods We used immunohistochemistry to identify tryptase(+) mast cells and CD68(+) macrophages in the tumor stroma and tumor islets in 175 patients with surgically resected NSCLC.Results Macrophages were detected in both the tumor stroma and islets in all patients. Mast cells were detected in the stroma and islets in 99.4% and 68.5% of patients, respectively. Using multivariate Cox proportional hazards analysis, increasing tumor islet macrophage density (P < .001) and tumor islet/stromal macrophage ratio (P < .001) emerged as favorable independent prognostic indicators. In contrast, increasing stromal macrophage density was an independent predictor of reduced survival (P = .001). The presence of tumor islet mast cells (P = .018) and increasing islet/stromal mast-cell ratio (P = .032) were also favorable independent prognostic indicators. Macrophage islet density showed the strongest effect: 5-year survival was 52.9% in patients with an islet macrophage density greater than the median versus 7% when less than the median (P < .0001). In the same groups, respectively, median survival was 2,244 versus 334 days (P < .0001). Patients with a high islet macrophage density but incomplete resection survived markedly longer than patients with a low islet macrophage density but complete resection.Conclusion The tumor islet CD68(+) macrophage density is a powerful independent predictor of survival from surgically resected NSCLC. The biologic explanation for this and its implications for the use of adjunctive treatment requires further study.