Figure 6

Pharmacological inhibition of SIRT2 enhances NK cell function and suppresses tumor progression. (a) Western blot showing decreased SIRT2 expression and deacetylase activity, as indicated by increased levels of α-tubulin K40 acetylation, in C57BL/6 mice treated with SirReal2, a small molecule SIRT2 inhibitor (n = 3). (b) Tumor progression and size were monitored up to 19 days following injection of B16-F10 cells into WT and Sirt2-KO mice treated with SirReal2 or vehicle (n = 12 and 18 for WT and Sirt2-KO). Two-way ANOVA with Bonferroni correction. (c) Tumors were harvested on Day 19 and weighed. (d) Subcutaneous melanoma tumors from WT mice were harvested and analyzed by flow cytometry for the prevalence of NK cells among leukocytes. The gating strategy was designed to identify NK cells as cells that are NKp46 positive and CD3E negative. (e) Abundance of NK cells as a percent of total leukocytes infiltrating melanoma tumors in WT (n = 10 and 8) and Sirt2-KO (n = 5) mice treated with vehicle or SirReal2 was quantified. (f) Absolute number of tumor-infiltrating NK cells in Sirt2-KI and WT mice. (c,e,f) One-way ANOVA with post-hoc Tukey HSD. Data points are mean values ± SEM. ***P < 0.001 and ****P < 0.0001.