Interleukin-7 Induces Differential Lymphokine-Activated Killer Cell Activity Against Human Melanoma Cells, Keratinocytes, and Endothelial Cells

To assess the potential role of interleukin (IL)-7 in immunotherapy of human malignant melanoma, we have examined the lymphokine-activated killer (LAK) cell sensitivity of four human melanoma cell lines against LAK cells generated by IL-7 or IL-2. Lysis was determined by a 24-h cytotoxicity test using 3-(4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT). All melanoma cell lines were susceptible to IL-7 – and IL-2 – generated LAK cells. The sensitivity of melanoma cells to IL-2 – induced LAK cells was higher compared to IL-7 – induced LAK cells. At an effector target ratio of 20 : 1, the lysis by IL-7 – induced LAK cells ranged between 41% and 52%, whereas IL-2 – induced lysis ranged between 80% and 94% (p < 0.01). IL-7-induced LAK cells, however, showed almost no cytotoxicity towards HaCat keratinocytes and human umbilical vein endothelial cells (HUVECs). Immunophenotyping revealed a higher expression of the tac antigen (CD 25) on IL-7-generated LAK cells, particularly those cells that were CD 56 negative or CD 3 positive compared to IL-2 – induced LAK cells. In contrast, IL-2 – generated LAK cells killed 62% of the HaCat keratinocytes and 60% of the HUVECs. Secretion of tumor necrosis factor-alpha into culture supernatants was significantly higher in IL-2-generated LAK cells compared to IL-7- stimulated LAK cells (p < 0.01), whereas TNF-alpha levels of IL-7 – induced LAK cells were in the range of unstimulated lymphocytes. Because nonspecific cytotoxicity against other normal cells such as keratinocytes and endothelial cells contributes to the dose-limiting side effects of immunotherapy with IL-2, immunotherapy using IL-7 might be a better tolerated future alternative.