Effect of OASL on oxaliplatin-induced immunogenic cell death in gastric cancer via the cGAS-STING signaling pathway

Abstract This study investigates the role of 2’-5’ oligoadenylate synthetase-like (OASL) in Oxaliplatin (OXA)-induced immunogenic cell death (ICD) in Gastric cancer (GC) cells through the cGAS-STING signaling pathway. Knockdown of OASL enhanced ICD expression, while overexpression had the opposite effect. mRNA sequencing of OASL-knockdown and control GC cells treated with OXA revealed significant enrichment of the cGAMP-mediated second messenger signaling pathway. cGAS synthesizes the second messenger molecule cGAMP, which directly activated STING. To clarify the mechanism, the role of OASL in OXA-induced ICD in GC cells was validated as mediated by the cGAS-STING signaling pathway. The Co-IP and immunofluorescence results confirmed that the OASL and cGAS proteins can bind directly. Further research using an in vivo mouse model validated these findings. Results show that OASL regulates OXA-induced ICD in GC cells via the cGAS-STING pathway, impacting chemosensitivity. The findings suggest new targets and strategies for improving GC therapy by modulating OASL expression to enhance OXA sensitivity through ICD mechanisms.