Interleukin-7 induces differential lymphokine-activated killer cell activity against human melanoma cells, keratinocytes, and endothelial cells

Abstract

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.