Fig. 4: ACAT inhibition boosts intratumoural and genetically engineered T cell responses.
From: Targeting human Acyl-CoA:cholesterol acyltransferase as a dual viral and T cell metabolic checkpoint
a–c Tumour-infiltrating leucocytes (TIL) from patients with HCC were stimulated with tumour-associated antigen (TAA; NY-ESO-1, MAGE-A1, AFP, HBc, HBs, Pol) OLP ±ACAT inhibition (K-604 or equivalent concentration of DMSO for 16 h) and IFNγ production of CD8+ T cells was detected by flow cytometry. The IFNγ production in wells without peptide stimulation was subtracted to determine TAA-specific IFNγ production in summary data. a Representative flow cytometry plot and summary data for each individual peptide pool (n = 20) in patients (n = 12) with detectable pre-existing TAA-specific CD8+ TIL responses. Brackets below the histogram indicate different OLP tested in TIL from the same patient. b Fold change of IFNγ production after stimulation with TAA OLP ±ACAT inhibition normalised to control without peptide stimulation. c IFNγ production of tissue-resident (CD103+CD69+) and non-resident (CD103−CD69−) CD8+ TIL ±ACAT inhibition. d, e IFNγ production (d) and specific target cell lysis (e) by HBcAg18-27 -TCR-gene-modified CD8+ T cells cocultured with HepG2-NTCP cells pulsed with increasing doses of C18 peptide (0.1 pM–50 pM) ±ACAT inhibition (Avasimibe or DMSO for 16 h). Representative data of four independent experiments. P values determined by Wilcoxon matched-pairs signed-rank test.
