Artesunate enhances gamma delta T-cell-mediated antitumor activity through augmenting gamma delta T-cell function and reversing immune escape of HepG2 cells

Objective: To explore the effect and mechanism of artesunate on gamma delta T cell-mediated antitumor immune responses against hepatoma carcinoma cells (HepG2) in vitro. Methods: Human gamma delta T cells or HepG2 were respectively treated with artesunate, subjected to co-culture as appropriate, and the following assays were subsequently conducted: CCK8 to examine cell viability; LDH release assay to detect the killing effect of gamma delta T cells on HepG2 cells; flow cytometry to examine the expression of perforin (PFP) and granzyme B (GraB) of gamma delta T cells; ELISA to evaluate the levels of TGF-beta 1 and IL-10 in the collected supernatant of HepG2 cells pretreated with artesunate; and Western blot analysis to examine Fas, FasL, STAT3, p-STAT3 expression of HepG2 cells induced by artesunate. Results: The results showed that the cytotoxicity effect of gamma delta T cells pretreated with artesunate on HepG2 cells was augmented via elevating the expression of GraB in gamma delta T cells. Furthermore, treatment with artesunate reversed the inhibition of HepG2 cells on gamma delta T cells by reducing the secretion of TGF-beta 1 in HepG2 cells supernatant and enhanced the antitumor effect of gamma delta T cells against HepG2 cells through increasing the expression of Fas on HepG2 cells, which may be attributed to the inhibition of STAT3 signaling protein. Conclusion: Artesunate has several mechanisms for augmenting the antitumor immune responses mediated by gamma delta T cells. These results suggested artesunate may be an efficacious agent in the treatment of hepatocellular carcinoma.