CYTOKINE PRODUCTION AND EXPRESSION OF ADHESION MOLECULES AND INTEGRINS IN TUMOR-INFILTRATING LYMPHOMONONUCLEAR CELLS OF NONSMALL CELL CARCINOMAS OF THE LUNG

Localization of intercellular adhesion molecule-1 and vascular cell ad hesion molecule-1, and of their ligands, lymphocyte function-associate d antigen-1 and very late activation antigen-4, was determined in non- small cell lung carcinomas and tumor-free lung. Messenger RNA expressi on for interleukins (IL) IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, tum or necrosis factor-alpha, transforming growth factor-beta, interferon- gamma, granulocyte-macrophages colony stimulating factor, and human pe rforin-1 was assessed by in situ hybridization on the same tissues. In tercellular adhesion mob ecule-1 was expressed in all blood vessels, w hereas only a low number ofvessels displayed vascular cell adhesion mo lecule-1 immunoreactivity. Tumor infiltrating lymphomononuclear cells consisted of lymphocyte function-associated antigen-1-positive cells a nd of a lower number of very fate activation antigen-4;positive cells. All squamous cell carcinomas consisted of intercellular adhesion mole cule-1-positive neoplastic cells infiltrated by lymphocyte function-as sociated antigen-1-positive tumor infiltrating lymphomononuclear and C D-la-positive Langerhans cells, whereas only a miller number of adenoc arcinomas displayed a consistent number of intercellular adhesion mole cule-1-positive neoplastic cells. Tumor infiltrating lymphomononuclear cells showed a wider production of cytokines when compared to bronchu s-associated lymphoid tissue of tumor-free lung. Moreover, cells produ cing interferon-gamma, IL-4, and IL-5 were more numerous ill squamous cell carcinomas than is adenocarcinomas. These findings indicate that the lung squamous cell carcinoma might represent a neoplastic microenv ironment able to induce activation of tumor infiltrating lymphomononuc lear cells more efficiently than the adenocarcinoma.