SOAT1 in ovarian cancer cells regulates immune response mediated by CD8⁺ T cells

Sterol-O acyltransferase 1 (SOAT1) functions by converting cholesterol and acyl-CoA into cholesterol ester and CoA-SH. SOAT1 inhibition suppresses tumor growth. A recent study has shown that inhibiting cholesterol esterification in T cells using genetic manipulation or drug treatment of SOAT1 boosted the cytotoxicity of CD8⁺ T cells. To better understand the role of SOAT1 in the tumor immune microenvironment of ovarian cancer (OC) and to optimize combined immunotherapy strategies, we examined the effect of SOAT1 manipulation and drug inhibition in OC cells on CD8⁺ T cell-mediated immune response in vitro.

Correlation analysis results obtained using GEPIA2 showed that SOAT1 expression was positively correlated with cytotoxic CD8⁺ T cell (CTL) infiltration levels and effector CD8⁺ T cell signature in OC. Additionally, the survival plot from the GSE26712 dataset indicated that CTLs provided clinical benefit in OC patients with high SOAT1 expression but not in those with low expression. The study findings also revealed that SOAT1 knockdown or avasimibe (SOAT1 inhibitor) treatment in OC cells resulted in the downregulation of IFN-γ secretion by CD8⁺ T cells in vitro. Interestingly, IL-6 and IL-8, two immunosuppressive cytokines known to promote CD8⁺ T cell dysfunction, were upregulated in SOAT1-silenced and avasimibe-treated OC cells.

In conclusion, the present study suggested that SOAT1 inhibition in OC cells could impair the cytotoxic capability of CD8⁺ T cells in vitro, probably through the increased secretion of IL-6 and IL-8 in OC cells.