title: Immune and Inflammatory Cell Composition of Human Lung Cancer Stroma.
abstract: Recent studies indicate that the abnormal microenvironment of tumors may play a critical role in carcinogenesis, including lung cancer. We comprehensively assessed the number of stromal cells, especially immune/inflammatory cells, in lung cancer and evaluated their infiltration in cancers of different stages, types and metastatic characteristics potential. Immunohistochemical analysis of lung cancer tissue arrays containing normal and lung cancer sections was performed. This analysis was combined with cyto-/histomorphological assessment and quantification of cells to classify/subclassify tumors accurately and to perform a high throughput analysis of stromal cell composition in different types of lung cancer. In human lung cancer sections we observed a significant elevation/infiltration of total-T lymphocytes (CD3+), cytotoxic-T cells (CD8+), T-helper cells (CD4+), B cells (CD20+), macrophages (CD68+), mast cells (CD117+), mononuclear cells (CD11c+), plasma cells, activated-T cells (MUM1+), B cells, myeloid cells (PD1+) and neutrophilic granulocytes (myeloperoxidase+) compared with healthy donor specimens. We observed all of these immune cell markers in different types of lung cancers including squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma, small cell carcinoma, papillary adenocarcinoma, metastatic adenocarcinoma, and bronchioloalveolar carcinoma. The numbers of all tumor-associated immune cells (except MUM1+ cells) in stage III cancer specimens was significantly greater than those in stage I samples. We observed substantial stage-dependent immune cell infiltration in human lung tumors suggesting that the tumor microenvironment plays a critical role during lung carcinogenesis. Strategies for therapeutic interference with lung cancer microenvironment should consider the complexity of its immune cell composition.
authors.affiliation: Internal Medicine, University of Giessen and Marburg Lung Center, Member of the German Center for Lung Research, Giessen, Germany.
authors.forename: G-Andre
authors.initials: GA
authors.lastname: Banat
authors.affiliation: Department of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Member of the German Center for Lung Research, Bad Nauheim, Germany.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Tretyn
authors.affiliation: Internal Medicine, University of Giessen and Marburg Lung Center, Member of the German Center for Lung Research, Giessen, Germany; Department of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Member of the German Center for Lung Research, Bad Nauheim, Germany.
authors.forename: Soni Savai
authors.initials: SS
authors.lastname: Pullamsetti
authors.affiliation: Internal Medicine, University of Giessen and Marburg Lung Center, Member of the German Center for Lung Research, Giessen, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Wilhelm
authors.affiliation: Institute of Biochemistry I, Goethe-University Frankfurt, Frankfurt, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Weigert
authors.affiliation: Institute of Biochemistry I, Goethe-University Frankfurt, Frankfurt, Germany.
authors.forename: Catherine
authors.initials: C
authors.lastname: Olesch
authors.affiliation: Department of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Member of the German Center for Lung Research, Bad Nauheim, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Ebel
authors.affiliation: Molecular Oncology, Philipps-University, Member of the German Center for Lung Research, Marburg, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Stiewe
authors.affiliation: Internal Medicine, University of Giessen and Marburg Lung Center, Member of the German Center for Lung Research, Giessen, Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Grimminger
authors.affiliation: Internal Medicine, University of Giessen and Marburg Lung Center, Member of the German Center for Lung Research, Giessen, Germany; Department of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Member of the German Center for Lung Research, Bad Nauheim, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Seeger
authors.affiliation: Institute of Pathology and Cytology, UEGP, Wetzlar, Germany.
authors.forename: Ludger
authors.initials: L
authors.lastname: Fink
authors.affiliation: Internal Medicine, University of Giessen and Marburg Lung Center, Member of the German Center for Lung Research, Giessen, Germany; Department of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Member of the German Center for Lung Research, Bad Nauheim, Germany.
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Savai
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology* / Q000473:pathology*; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology*; D009195:Peroxidase / Q000378:metabolism; D017154:Stromal Cells / Q000473:pathology; D059016:Tumor Microenvironment
chemical_list: D015703:Antigens, CD; D009195:Peroxidase