Endogenous double-stranded RNA: Bridging immune activation and cancer therapeutics

Although it was previously believed that double-stranded RNAs (dsRNAs) were exclusively associated with viral infections, accumulating evidence indicates that dsRNAs can also arise from endogenous sources. Given the innate immunogenicity of dsRNAs, mammalian cells have evolved mechanisms to prevent the accumulation of intracellular dsRNAs, as their presence can provoke an interferon (IFN) response, which could potentially lead to an immune reaction against tumor cells. This implies that stimulating dsRNA production and enhancing dsRNA sensing may represent a promising strategy for anti-tumor therapies by triggering a strong immune response. Despite recent research identifying numerous dsRNA sensors and effectors, the specific roles and regulatory mechanisms of dsRNA in the development and progression of cancer remain to be fully understood. This review provides an overview of the mechanisms by which endogenous dsRNA is generated in mammalian cells, its role in immune activation, and its potential applications in cancer immunotherapy, aiming to advance the translational research of dsRNA from immune activation to cancer treatment.