Cytokine production and expression of adhesion molecules and integrins in tumor infiltrating lymphomononuclear cells of non-small cell carcinomas of the lung.

Localization of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and of their ligands, lymphocyte function-associated antigen-1 and very late activation antigen-4, was determined in non-small cell lung carcinomas and tumor-free lung. Messenger RNA expression for interleukins (IL) IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, tumor necrosis factor-alpha, transforming growth factor-beta, interferon-gamma, granulocyte-macrophages colony stimulating factor, and human perforin-1 was assessed by in situ hybridization on the same tissues. Intercellular adhesion molecule-1 was expressed in all blood vessels, whereas only a low number of vessels displayed vascular cell adhesion molecule-1 immunoreactivity. Tumor infiltrating lymphomononuclear cells consisted of lymphocyte function-associated antigen-1-positive cells and of a lower number of very late activation antigen-4-positive cells. All squamous cell carcinomas consisted of intercellular adhesion molecule-1-positive neoplastic cells infiltrated by lymphocyte function-associated antigen-1-positive tumor infiltrating lymphomononuclear and CD-la-positive Langerhans cells, whereas only a minor number of adenocarcinomas displayed a consistent number of intercellular adhesion molecule-1-positive neoplastic cells. Tumor infiltrating lymphomononuclear cells showed a wider production of cytokines when compared to bronchus-associated lymphoid tissue of tumor-free lung. Moreover, cells producing interferon-gamma, IL-4, and IL-5 were more numerous in squamous cell carcinomas than in adenocarcinomas. These findings indicate that the lung squamous cell carcinoma might represent a neoplastic microenvironment able to induce activation of tumor infiltrating lymphomononuclear cells more efficiently than the adenocarcinoma.