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RESEARCH PRODUCT

Interleukin-2 and its Receptors in Human Solid Tumours: Immunobiology and Clinical Significance

subject

description

Human carcinomas were found to express IL-2 R and to produce, but not to secrete, IL-2. Intermediate affinity IL-2Rβγ detected on the surface and in the cytoplasm of carcinoma cells binds exogenous IL-2 at the nanomolar or micromolar concentrations and mediates cell cycle arrest (CCA) possibly through the upregulation of the CDK inhibitor p27kipl expression. In contrast, IL-2Rα is modestly expressed on the cell surface, and it may be involved in the intracrine pathway of delivering endogenous IL-2 to the cell surface. IL-2 is a growth factor for human carcinomas, and as it binds to the high-affinity IL-2R, it promotes cellular proliferation by suppressing expression of p27kipl. It also protects tumour cells from apoptosis. The presence in carcinomas and in normal tissue cells of two IL-2/IL-2R pathways regulating cellular growth and survival is a novel finding. Both the endogenous and exogenous IL2/IL2R pathways could become therapeutic targets in the future and could be explored to obtain insights into the mechanisms of tumour growth control as well as to modulate its sensitivity to other therapies.