This study explores the regulatory role of 2'-5' oligoadenylate synthetase-like (OASL) in modulating oxaliplatin (OXA)-induced immunogenic cell death (ICD) in gastric cancer (GC) via the cGAS-STING signaling pathway. Silencing OASL resulted in increased ICD expression, whereas its overexpression suppressed these effects. Transcriptomic profiling of OASL-knockdown and control GC cells treated with OXA demonstrated marked enrichment in the cGAMP-mediated second messenger pathway. As a key upstream enzyme, cGAS generates the second messenger cGAMP, which directly activates STING. Mechanistic investigations confirmed that OASL regulates OXA-induced ICD in GC cells through the cGAS-STING pathway. Co-immunoprecipitation and immunofluorescence assays revealed a direct interaction between OASL and cGAS proteins. These findings were further corroborated in an in vivo mouse model. Collectively, the data indicate that OASL modulates OXA-induced ICD via cGAS-STING, influencing chemosensitivity, and highlight OASL as a potential target for enhancing OXA efficacy in GC treatment.
