Role of the cGAS-STING pathway in CIK cell therapy

The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is an innate immune response activated by the sensing of cytosolic double-stranded DNA. The activation of the pathway leads to the expression of pro-inflammatory cytokines which trigger the activation of the immune system. Previous studies have demonstrated that the activation of the cGAS-STING pathway in cancer cells promotes antitumor immunity and increases the survival time of the patient by inducing cancer cells’ senescence and apoptosis and enhancing the infiltration of immune cells in the tumor microenvironment. Since cancer cells evolved to avoid the activation of the cGAS-STING pathway we tried to stimulate its activation via the treatment of MCF-7 breast cancer cells with ADU-S100, a STING agonist, to see whether it would lead to the activation of the pathway and to a consequent increase in the antitumor activity of adoptive CIK cells treatment. MCF-7 cells’ phenotype was obtained via flow cytometry and the cytotoxic activity of CIK cells against the target was assessed through a calcein-AM cytotoxic assay. We demonstrated that the treatment of MCF-7 breast cancer cells with different concentrations of ADU-S100 leads to an increase in the surface expression of multiple NKG2D ligands thus increasing CIK cells’ antitumor activity.