Alginate sulfated polysaccharide TGC161 exhibits antitumor activity via suppression of STING activation-mediated T-cell apoptosis

The clinical interest in utilizing stimulators of interferon genes (STING) agonists and inhibitors as anticancer drugs is substantial. Alginate sulfated polysaccharide TGC161 can mitigate T-cell apoptosis, thus ameliorating chemotherapy-induced leukopenia. We investigated the effect of TGC161 on the T-cell apoptosis induced by STING activation. TGC161 negatively regulated the STING-TBK1-IRF3 signaling pathway by inhibiting the expression of phosphorylated IRF3 protein. TGC161 could suppress T-cell apoptosis by inhibiting protein expression of cleaved caspase-3 and PARP. TGC161 promoted the number of immune cells in peripheral blood, thereby enhancing antitumor capabilities. Our data suggest that TGC161 could have potent and novel antitumor activities, thereby rendering it an attractive candidate for clinical therapy. TGC161 inhibited CARB-mediated activation of the STING-TBK1-IRF3 signaling pathway and reduced mRNA expression of interferon-associated cytokines in T cells.TGC161 inhibited T-cell apoptosis by inhibiting mRNA expression of the pro-apoptotic genes bik and noxa . TGC161 increased the survival of and infiltration by T cells by inhibiting STING activation-induced T-cell apoptosis and ultimately enhanced antitumor ability. TGC161 did not significantly inhibit STING in macrophages but promoted the infiltration of macrophages to enhance antitumor ability.