Abstract
Interleukin 15 (IL-15) is a novel cytokine that shares no homology with IL-2, but it requires the use of β and γ chains of the IL-2 receptor complex for binding and signaling. In vitro studies have shown induction of CTL and lymphokine-activated killer (LAK) cell activity in peripheral blood mononuclear cells (PBMCs) from normal donors by IL-15 against known tumor targets. The present study attempts to define the role of IL-15 in generating LAK activity from melanoma patient lymphocytes. PBMCs of patients newly diagnosed with metastatic melanoma were incubated with different doses of recombinant human IL-15 and tested against autologous tumor cells, LAK sensitive cell lines (i,e., FMEX and Daudi), as well as the natural killer-sensitive cell line K562, in a 15-h 51Cr release assay. The effect of IL-15 was found to be both time and dose dependent, with peak activity detected after 2 or 3 days of culture with 100 ng/ml of this cytokine. LAK and not CTL activity in patient PBMCs was detected by the inability of mAbs against CD4, CD8, and MHC class I to effectively block lysis of autologous tumor and FMEX melanoma cells. In addition, interaction via the CD18 adhesion molecule was shown to be critical in IL-15-induced LAK-mediated lysis of autologous tumor cells. Finally, incubation of patient PBMCs with IL-15 for 6 h resulted in the up-regulation of perforin mRNA transcription. These findings suggest that LAK activity can be generated from melanoma patient PBMCs in the presence of IL-15 to lyse autologous tumor cells in a non-MHC-restricted manner. This new cytokine may play an important role in antitumor immunity with a possible use for cancer immunotherapy.
Original language | English |
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Pages (from-to) | 4988-4994 |
Number of pages | 7 |
Journal | Cancer Research |
Volume | 55 |
Issue number | 21 |
State | Published - Nov 1 1995 |
Keywords
- Biopsy
- CD18 Antigens/physiology
- Humans
- Immunotherapy
- Interleukin-15
- Interleukins/pharmacology
- Killer Cells, Lymphokine-Activated/drug effects
- Lymphocyte Activation/drug effects
- Lymphocytes/drug effects
- Melanoma/immunology
- Membrane Glycoproteins/genetics
- Sensitivity and Specificity
- Stimulation, Chemical
- Transcription, Genetic