title: Alveolar macrophage function is altered in patients with lung cancer.
abstract: 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.
authors.affiliation: Immunology and Vaccine Laboratory, Austin Research Institute, Heidelberg, Victoria, Australia.
authors.forename: D S
authors.initials: DS
authors.lastname: Pouniotis
authors.forename: M
authors.initials: M
authors.lastname: Plebanski
authors.forename: V
authors.initials: V
authors.lastname: Apostolopoulos
authors.forename: C F
authors.initials: CF
authors.lastname: McDonald
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D018287:Carcinoma, Large Cell / Q000276:immunology; D018288:Carcinoma, Small Cell / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D037181:Lectins, C-Type / Q000032:analysis; D008175:Lung Neoplasms / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000032:analysis; D008562:Membrane Glycoproteins / Q000032:analysis; D008863:Microspheres; D008875:Middle Aged; D010641:Phenotype; D011137:Polystyrenes / Q000493:pharmacokinetics; D011650:Pulmonary Alveoli / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000032:analysis; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D016207:Cytokines; D006684:HLA-DR Antigens; D007136:Immunoglobulins; D018799:Intercellular Adhesion Molecule-1; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins; D011137:Polystyrenes; D011956:Receptors, Cell Surface; D000097802:CD83 Antigen