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

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

Immunopharmacol Immunotoxicol. 2018 Feb 06;:1-10

Authors: Qian P, Zhang YW, Zhou ZH, Liu JQ, Yue SY, Guo XL, Sun LQ, Lv XT, Chen JQ

Abstract
OBJECTIVE: To explore the effect and mechanism of artesunate on γδ T cell-mediated antitumor immune responses against hepatoma carcinoma cells (HepG2) in vitro.
METHODS: Human γδ 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 γδ T cells on HepG2 cells; flow cytometry to examine the expression of perforin (PFP) and granzyme B (GraB) of γδ T cells; ELISA to evaluate the levels of TGF-β1 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 γδ T cells pretreated with artesunate on HepG2 cells was augmented via elevating the expression of GraB in γδ T cells. Furthermore, treatment with artesunate reversed the inhibition of HepG2 cells on γδ T cells by reducing the secretion of TGF-β1 in HepG2 cells supernatant and enhanced the antitumor effect of γδ 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 γδ T cells. These results suggested artesunate may be an efficacious agent in the treatment of hepatocellular carcinoma.

PMID: 29405080 [PubMed - as supplied by publisher]

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