NK cell activation and metabolic modulation in response to different stimuli
| Stimuli . | Dosage . | NK cell response . | Source of NK cells . | Reference . |
|---|---|---|---|---|
| High-dose or low-dose IL-12 and IL-18 | IL-12 (1 ng/ml), IL-18 (1 ng/ml); or IL-12 (10 ng/ml), IL-18 (50 ng/ml) | Activation and IFN-γ production independent of glycolysis or OXPHOS | Splenocytes (murine) | Keppel et al., 2015 |
| Anti-NK1.1 or anti-Ly49D | 20 μg/ml | Activation and IFN-γ production dependent on glycolysis and OXPHOS | Splenocytes (murine) | Keppel et al., 2015 |
| High-dose IL-15 and anti-NK1.1 or anti-Ly49D | IL-15 (100 ng/ml), anti-NK1.1, or anti-Ly49D (20 μg/ml) | Activation and IFN-γ production independent of glycolysis or OXPHOS | Splenocytes (murine) | Keppel et al., 2015 |
| High-dose IL-15 | IL-15 (100 ng/ml) or IL-15/IL-15Rα complex (50 or 100 ng/ml) | Activation, IFN-γ production, and increased metabolic profile (glycolysis and OXPHOS) dependent on mTOR signaling | Splenocytes (murine) | Marçais et al., 2014; Nandagopal et al., 2014 |
| Low-dose IL-15 | IL-15 (10 ng/ml) or IL-15/IL-15Rα complex (10 ng/ml) | Cell survival and viability dependent on STAT5 phosphorylation | Splenocytes (murine) | Marçais et al., 2014; Nandagopal et al., 2014 |
| IL-2 and IL-12 | IL-2 (20 ng/ml), IL-12 (10 ng/ml) | Activation and IFN-γ production; increased metabolic profile (glycolysis and OXPHOS) independent of glutamine-fueled TCA cycle; increased cMyc expression dependent on glutamine availability and SLC7A5 activity | Splenocytes (murine) | Loftus et al., 2018 |
| IL-12, IL-15, and IL-18 (CIML NK cells) | IL-12 (10 ng/ml), IL-15 (10 ng/ml), IL-18 (50 ng/ml) | More IFN-γ production after re-stimulated by IL-12 (10 ng/ml) and IL-15 (100 ng/ml) or anti-Ly49H or anti-NK1.1 (5 μg/ml) | Splenocytes (murine) | Cooper et al., 2009 |
| IL-12 (10 ng/ml), IL-15 (100 ng/ml), IL-18 (50 ng/ml) | More IFN-γ production after re-stimulated by IL-12/15/18 (10, 100, 50 ng/ml, respectively) or K562 cells; shift towards glycolysis upon activation with short-term increased OXPHOS; increased expression of nutrient transporters (CD98 and GLUT1) | PBMC (human) | Terrén et al., 2021 | |
| IL-12 and IL-15 | IL-12 (30 ng/ml), IL-15 (100 ng/ml) | Activation and IFN-γ production dependent on elevated OXPHOS; upregulated glycolysis and OXPHOS insensitive to rapamycin | PBMC (human) | Keating et al., 2016 |
| IL-2 | 500 U/ml | Activation and IFN-γ production dependent on elevated OXPHOS; upregulated glycolysis and OXPHOS dependent on mTORC1 | PBMC (human) | Keating et al., 2016 |
| IL-2 and anti-NKG2D | IL-2 (200 U/ml), anti-NKG2D (5 μg/ml) | Activation and IFN-γ production; upregulated expression of SLC1A5 and CD98 mediated by mTORC1 (a prerequisite of following NKG2D-mediated activation) | PBMC (human) | Jensen et al., 2017 |
| Stimuli . | Dosage . | NK cell response . | Source of NK cells . | Reference . |
|---|---|---|---|---|
| High-dose or low-dose IL-12 and IL-18 | IL-12 (1 ng/ml), IL-18 (1 ng/ml); or IL-12 (10 ng/ml), IL-18 (50 ng/ml) | Activation and IFN-γ production independent of glycolysis or OXPHOS | Splenocytes (murine) | Keppel et al., 2015 |
| Anti-NK1.1 or anti-Ly49D | 20 μg/ml | Activation and IFN-γ production dependent on glycolysis and OXPHOS | Splenocytes (murine) | Keppel et al., 2015 |
| High-dose IL-15 and anti-NK1.1 or anti-Ly49D | IL-15 (100 ng/ml), anti-NK1.1, or anti-Ly49D (20 μg/ml) | Activation and IFN-γ production independent of glycolysis or OXPHOS | Splenocytes (murine) | Keppel et al., 2015 |
| High-dose IL-15 | IL-15 (100 ng/ml) or IL-15/IL-15Rα complex (50 or 100 ng/ml) | Activation, IFN-γ production, and increased metabolic profile (glycolysis and OXPHOS) dependent on mTOR signaling | Splenocytes (murine) | Marçais et al., 2014; Nandagopal et al., 2014 |
| Low-dose IL-15 | IL-15 (10 ng/ml) or IL-15/IL-15Rα complex (10 ng/ml) | Cell survival and viability dependent on STAT5 phosphorylation | Splenocytes (murine) | Marçais et al., 2014; Nandagopal et al., 2014 |
| IL-2 and IL-12 | IL-2 (20 ng/ml), IL-12 (10 ng/ml) | Activation and IFN-γ production; increased metabolic profile (glycolysis and OXPHOS) independent of glutamine-fueled TCA cycle; increased cMyc expression dependent on glutamine availability and SLC7A5 activity | Splenocytes (murine) | Loftus et al., 2018 |
| IL-12, IL-15, and IL-18 (CIML NK cells) | IL-12 (10 ng/ml), IL-15 (10 ng/ml), IL-18 (50 ng/ml) | More IFN-γ production after re-stimulated by IL-12 (10 ng/ml) and IL-15 (100 ng/ml) or anti-Ly49H or anti-NK1.1 (5 μg/ml) | Splenocytes (murine) | Cooper et al., 2009 |
| IL-12 (10 ng/ml), IL-15 (100 ng/ml), IL-18 (50 ng/ml) | More IFN-γ production after re-stimulated by IL-12/15/18 (10, 100, 50 ng/ml, respectively) or K562 cells; shift towards glycolysis upon activation with short-term increased OXPHOS; increased expression of nutrient transporters (CD98 and GLUT1) | PBMC (human) | Terrén et al., 2021 | |
| IL-12 and IL-15 | IL-12 (30 ng/ml), IL-15 (100 ng/ml) | Activation and IFN-γ production dependent on elevated OXPHOS; upregulated glycolysis and OXPHOS insensitive to rapamycin | PBMC (human) | Keating et al., 2016 |
| IL-2 | 500 U/ml | Activation and IFN-γ production dependent on elevated OXPHOS; upregulated glycolysis and OXPHOS dependent on mTORC1 | PBMC (human) | Keating et al., 2016 |
| IL-2 and anti-NKG2D | IL-2 (200 U/ml), anti-NKG2D (5 μg/ml) | Activation and IFN-γ production; upregulated expression of SLC1A5 and CD98 mediated by mTORC1 (a prerequisite of following NKG2D-mediated activation) | PBMC (human) | Jensen et al., 2017 |
CIML, cytokine-induced memory-like; SLC7A5, solute carrier family 7 member 5; SLC1A5, solute carrier family 1 member 5.