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. 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.
Highlights
Lung cancer is a highly aggressive and challenging disease and is the leading cause of cancer mortality worldwide
Infiltration of T lymphocytes into human lung tissue was assessed by immunohistochemical analysis using the CD3 antibody
The infiltration of CD3+ T lymphocytes was independent of cancer type (Fig 2B and 2F), but the number of infiltrating cells was higher in later stages of lung cancer [173 (151. . .199) stage III vs. 61(33. . .114) stage I lung cancer, Fig 2C]
Summary
Lung cancer is a highly aggressive and challenging disease and is the leading cause of cancer mortality worldwide. 80–85% of all lung cancer patients are treated with one or more options within a standard regimen that involves surgery, radiation therapy, and chemotherapy with disease stage determining the therapeutic options These treatments have produced promising results as neo-adjuvant and adjuvant strategies for early-stage patients and for treatment of locally advanced and advanced disease, treatment outcomes for lung cancer are still considered disappointing. This is largely due to a delay in diagnosis and inadequate knowledge about tumor progression and its associated molecular alterations [3]. These techniques were combined with cyto-/histomorphological assessment and quantification of the cells, to classify/subclassify tumors accurately and high throughput analysis of stromal cell composition in different types of lung cancer
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