mTOR contributes to IL-15–associated protective and metabolic benefits in human NK cells. Freshly isolated primary human NK cells were activated with IL-2 or IL-15 for 48 hours in the presence of DMSO or the selective mTOR inhibitor torin-1 (1 μM). (A) The real-time OCR (picomoles per minute) and glycolysis rate (ECAR; milli-pH per minute) were measured using the Seahorse platform. (B) The impact of torin-1 on frequency and expression intensity of CD25 was measured on NK cells by FACS. (C) Expression levels of membrane-bound cytokines or IL-15Rα chain as determined by FACS. (D) Lysis of K562 cells mediated by IL-15–activated NK cells, in the presence of torin-1 (filled symbols), DMSO (open symbols) after direct activation or following cytokine withdrawal. Shaded symbols show lysis of K562 cells by IL-2–activated NK cells after cytokine withdrawal in the presence of DMSO. Results from multiple donors (n > 4) were summarized and presented as mean ± SD. Representative histograms were chosen based on proximity to average values. *P < .05; **P < .01; ***P < .001; Mann-Whitney nonparametric U test. FCCP, carbonyl cyanide-p-trifluoromethoxyphenylhydrazone; Gluc, glucose.