Interleukin 15 Induction of Lymphokine-activated Killer Cell Function against Autologous Tumor Cells in Melanoma Patient Lymphocytes by a CD18-Dependent, Perforin-related Mechanism

Julie Y. Djeu, Ana M. Gamero, Douglas S. Reintgen, Christopher A. Puleo, Dewayne Ussery, Julie Y. Djeu

Research output: Contribution to journalArticlepeer-review

90 Scopus citations

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 languageEnglish
Pages (from-to)4988-4994
Number of pages7
JournalCancer Research
Volume55
Issue number21
StatePublished - 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

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