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 language | English |
|---|---|
| Pages (from-to) | 5594-5599 |
| Number of pages | 6 |
| Journal | Cancer Research |
| Volume | 67 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Jun 15 2007 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Membrane-bound interleukin (IL)-15 on renal tumor cells rescues natural killer cells from IL-2 starvation-induced apoptosis. / Wittnebel, Sebastian; Da Rocha, Sylvie; Giron-Michel, Julien; Jalil, Abdelali; Opolon, Paule; Escudier, Bernard; Validire, Pierre; Khawam, Krystel; Chouaib, Salem; Azzarone, Bruno; Caignard, Anne.
In: Cancer Research, Vol. 67, No. 12, 15.06.2007, p. 5594-5599.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Membrane-bound interleukin (IL)-15 on renal tumor cells rescues natural killer cells from IL-2 starvation-induced apoptosis
AU - Wittnebel, Sebastian
AU - Da Rocha, Sylvie
AU - Giron-Michel, Julien
AU - Jalil, Abdelali
AU - Opolon, Paule
AU - Escudier, Bernard
AU - Validire, Pierre
AU - Khawam, Krystel
AU - Chouaib, Salem
AU - Azzarone, Bruno
AU - Caignard, Anne
PY - 2007/6/15
Y1 - 2007/6/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=34347233859&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34347233859&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-06-4406
DO - 10.1158/0008-5472.CAN-06-4406
M3 - Article
C2 - 17575122
AN - SCOPUS:34347233859
VL - 67
SP - 5594
EP - 5599
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 12
ER -