Therapeutic targeting of TI suppresses inflammation in ECD. (A) FDG-PET studies showing uptake of glucose by ECD lesions at baseline (left) and after clinical treatment with the selective BRAFV600E inhibitor vemurafenib (VEM) at a dose of 480 mg daily for 3 months. (B) Details from the FDG-PET evaluation shown in panel A: femoral (top panel), retroperitoneal (middle panel), and pineal (bottom panel, arrow) lesions. (C) Serum cytokines before and after therapeutic inhibition of BRAFV600E with VEM at a dose of 480 mg daily for 3 months. Data are the mean ± SEM (n = 4); *P < .05, Mann-Whitney U test. (D) Metabolomics analysis on supernatants of an ECD lesion (skin biopsy specimen) cultured in bioreactor in the presence or absence of the MAPK pathway inhibitor (MAPKi) trametinib (GSK1120212, 1 nM); supernatants were retrieved for metabolite determination after 4 days of culture. TCM: tissue culture medium (baseline comparison). (E) Cytokine production measured in the supernatant of nontransduced macrophages (UT) or macrophages expressing BRAFV600E (VE) cultured in the presence or absence of different treatments for 48 hours. 2DG, glycolysis inhibitor; BPTES, bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (glutaminolysis inhibitor). Data are shown as means ± SEM (n = 6); biological duplicates were performed for each condition. **P < .01; ***P < .001; ****P < .0001, paired Student t test.