Membrane-Bound Interleukin (IL)-15 on Renal Tumor Cells Rescues Natural Killer Cells from IL-2 Starvation-Induced Apoptosis. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Cancer Research Année : 2007

Membrane-Bound Interleukin (IL)-15 on Renal Tumor Cells Rescues Natural Killer Cells from IL-2 Starvation-Induced Apoptosis.

Sebastian Wittnebel
  • Fonction : Auteur
Sylvie da Rocha
  • Fonction : Auteur
Julien Giron-Michel
Abdelali Jalil
  • Fonction : Auteur
Pierre Validire
  • Fonction : Auteur
Krystel Khawam
  • Fonction : Auteur
Bruno Azzarone
  • Fonction : Auteur
Anne Caignard
  • Fonction : Auteur

Résumé

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 alpha (IL-15Ralpha). Silencing of IL-15Ralpha 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-15Ralpha 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-15Ralpha 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. [Cancer Res 2007;67(12):5594-9].
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Dates et versions

hal-00158208 , version 1 (28-06-2007)

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Citer

Sebastian Wittnebel, Sylvie da Rocha, Julien Giron-Michel, Abdelali Jalil, Paule Opolon, et al.. Membrane-Bound Interleukin (IL)-15 on Renal Tumor Cells Rescues Natural Killer Cells from IL-2 Starvation-Induced Apoptosis.. Cancer Research, 2007, 67 (12), pp.5594-9. ⟨10.1158/0008-5472.CAN-06-4406⟩. ⟨hal-00158208⟩
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