Immune and Inflammatory Cell Composition of Human Lung Cancer Stroma
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. Immunohistochemical analysis of lung cancer tissue arrays containing normal and lung cancer sections was performed. Cells positive for specific markers were counted within whole sections. 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 and activated T-cells (MUM1+), activated T-cells, B-cells, and 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 in stage-III cancer specimens significantly surpassed 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.