ARE INTERLEUKIN-2 AND INTERLEUKIN-15 TUMOR-PROMOTING FACTORS FOR HUMAN NONHEMATOPOIETIC CELLS

Human normal non hematopoietic cells of mesenchymal and neuroectoderma l origin may express functional IL-Rs. For instance, in these cell typ es, IL-2 can stimulate proliferation (endothelial, intestinal and nerv ous cells) or modify the expression of adhesion molecules (fibroblasts ) or inhibit proliferation (bone marrow stromal cells), Therefore, som e cytotoxic effects described during IL-2 biotherapy could be due to a direct interaction between IL-2 and non-hematopoietic tissues. The ex pression of functional IL-2-R has also been reported in several human cell lines derived from solid tumors, In some instances IL-2 inhibits cell growth (head and neck, gastric and renal carcinomas), but in othe r tumors, growth stimulation and increased expression of markers of tu mor progression have been reported (intestinal, breast, and lung carci nomas, gliomas, fibrosarcomas and melanomas), Additionally, secretion of biologically active IL-2 has been reported in some melanoma and bre ast cancer cell lines. Transcripts for the novel cytokine IL-15, which utilizes the beta and gamma chains of the IL2-R, have been found in m elanoma cells and anti-IL-15 mabs inhibit HLA class I expression in th ese cells, Therefore these cytokines may modify, inside a tumor, the b ehavior of both stromal and neoplastic cells, All these data may have important implications in our understanding of tumor host interactions and in future strategies of immunotherapy.