Membrane-bound interleukin (IL)-15 on renal tumor cells rescues natural killer cells from IL-2 starvation-induced apoptosis

Sebastian Wittnebel, Sylvie Da Rocha, Julien Giron-Michel, Abdelali Jalil, Paule Opolon, Bernard Escudier, Pierre Validire, Krystel Khawam, Salem Chouaib, Bruno Azzarone, Anne Caignard

Research output: Contribution to journalArticle

Abstract

Renal cell carcinoma primary tumors and lung metastases are infiltrated by activated natural killer (NK) cells. Interleukin (IL)-15,a major cytokine involved in cross-talk between accessory cells (dendritic cells and macrophages) and NK cells,is produced by epithelial renal cells. We show that renal cell carcinoma cells and normal renal cells express IL-15 mRNA and membrane-bound IL-15 (MbIL-15). These cells also express IL-15 receptor α (IL-15Rα). Silencing of IL-15Rα by specific small interfering RNA in renal cell carcinoma had no effect on MbIL-15 production,indicating that the cytokine is not cross-presented by IL-15Rα in renal cell carcinoma cells but anchored to the membrane. Furthermore,we show that MbIL-15 from renal cell carcinoma cells is functional and involved in rapid nuclear translocation of phosphorylated signal transducers and activators of transcription 3 in IL-2-starved NK cells. MbIL-15 on the target did not interfere with resting NK cell activation and target cell cytolysis but rescued NK cells from IL-2 starvation-induced apoptosis through contact-dependent interaction. Masking of MbIL-15 with soluble IL-15Rα molecules restored NK cell apoptosis. These findings suggest that IL-15 produced by renal tumor cells is involved in the maintenance of active NK cells at the tumor site.

Original languageEnglish
Pages (from-to)5594-5599
Number of pages6
JournalCancer Research
Volume67
Issue number12
DOIs
Publication statusPublished - Jun 15 2007

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Wittnebel, S., Da Rocha, S., Giron-Michel, J., Jalil, A., Opolon, P., Escudier, B., Validire, P., Khawam, K., Chouaib, S., Azzarone, B., & Caignard, A. (2007). Membrane-bound interleukin (IL)-15 on renal tumor cells rescues natural killer cells from IL-2 starvation-induced apoptosis. Cancer Research, 67(12), 5594-5599. https://doi.org/10.1158/0008-5472.CAN-06-4406