Pouniotis D S, Plebanski M, Apostolopoulos V, McDonald C F
Immunology and Vaccine Laboratory, Austin Research Institute, Heidelberg, Victoria, Australia.
Clin Exp Immunol. 2006 Feb;143(2):363-72. doi: 10.1111/j.1365-2249.2006.02998.x.
The alveolar macrophage (AM) is believed to be of central importance in the immune response against infection and tumour. We examined patients with lung cancer in order to evaluate the immuno-stimulatory potential of AM in lung cancer. Bronchoalveolar lavage fluid samples were obtained from patients with adenocarcinoma, squamous cell carcinoma, large cell undifferentiated lung carcinoma, small cell carcinoma and control subjects. AM were isolated and phagocytic function, flow cytometry and cytokine analysis were assessed. AM from patients with small and squamous cell carcinoma had impaired uptake in vitro of 40 nm fluorescent polystyrene beads. AM from patients with small, squamous and large cell undifferentiated carcinoma showed impaired uptake of 1000 nm fluorescent polystyrene beads. Secreted levels of TNF-alpha and IL-1 from AM of patients with small, squamous, and large cell undifferentiated carcinoma were decreased compared to controls. Secreted AM IL-6 levels were decreased in small and large cell undifferentiated carcinoma. AM from adenocarcinoma patients showed similar levels of IL-10, IL-6, IL-1 and TNF-alpha compared to controls. Phenotypic analysis demonstrated that patients with small cell carcinoma were the only group that showed a decrease in MHC class II surface expression. Surface expression of ICAM-1 and CD83 was decreased on AM from patients with large, squamous and small cell carcinoma compared to controls but not adenocarcinoma. Mannose receptor levels were only decreased on AM from patients with squamous and small cell carcinoma but not adenocarcinoma and large cell undifferentiated carcinoma. We conclude that there are type-specific alterations in uptake ability, cytokine secretion and phenotype of AM from lung cancer patients, which may result in an inability to stimulate anti-tumour immunity. The observed differences between lung cancer subgroups may explain previously reported inconsistencies in descriptions of AM characteristics in lung cancer.
肺泡巨噬细胞(AM)被认为在针对感染和肿瘤的免疫反应中至关重要。我们对肺癌患者进行了检查,以评估AM在肺癌中的免疫刺激潜力。从腺癌、鳞状细胞癌、大细胞未分化肺癌、小细胞癌患者及对照受试者中获取支气管肺泡灌洗液样本。分离出AM并评估其吞噬功能、流式细胞术及细胞因子分析。小细胞癌和鳞状细胞癌患者的AM在体外对40纳米荧光聚苯乙烯珠的摄取受损。小细胞癌、鳞状细胞癌和大细胞未分化癌患者的AM对1000纳米荧光聚苯乙烯珠的摄取受损。与对照组相比,小细胞癌、鳞状细胞癌和大细胞未分化癌患者的AM分泌的肿瘤坏死因子-α(TNF-α)和白细胞介素-1(IL-1)水平降低。小细胞癌和大细胞未分化癌患者的AM分泌的IL-6水平降低。腺癌患者的AM分泌的IL-10、IL-6、IL-1和TNF-α水平与对照组相似。表型分析表明,小细胞癌患者是唯一一组主要组织相容性复合体II类(MHC class II)表面表达降低的人群。与对照组相比,大细胞癌、鳞状细胞癌和小细胞癌患者的AM表面细胞间黏附分子-1(ICAM-1)和CD83的表达降低,但腺癌患者无此现象。甘露糖受体水平仅在鳞状细胞癌和小细胞癌患者的AM上降低,腺癌和大细胞未分化癌患者的AM上未降低。我们得出结论,肺癌患者的AM在摄取能力、细胞因子分泌和表型方面存在类型特异性改变,这可能导致无法刺激抗肿瘤免疫。肺癌亚组之间观察到的差异可能解释了先前报道的肺癌中AM特征描述不一致的情况。