Researchers at Baylor College of Medicine (USA) have discovered how therapies targeting RNA splicing can activate antiviral immune pathways in triple negative breast cancers (TNBC) to trigger tumor cell death and activate the body’s immune response.
A new study, published in the journal ‘Cell’, shows that mis-spliced endogenous RNA in tumor cells mimics an RNA virus, causing tumor cells to self-destruct as if they were fighting an infection. “We know that therapies that partially interfere with RNA splicing can have a very strong impact on tumor growth and progression, but the mechanisms of tumor destruction are largely unknown. In this study, we found that these therapies are modulatory. of antitumor immunity “, have asserted the experts.
Westbrook’s team wanted to understand how these drugs interfere with tumor progression, thus noting that in TNBC cells, spliceosome-targeted therapies interfere with RNA splicing and cause an accumulation of mis-spliced endogenous intron RNA in the cytoplasm of the tumor cell.
Many of those aberrant RNAs will form double-stranded structures, like an RNA virus. Antiviral immune pathways recognize double-stranded RNA and then trigger apoptosis and send signals to the body’s immune system to elicit an inflammatory response.
These discoveries may also lead to new biomarkers to select patients who respond to current immunomodulatory therapies. Specifically, research suggests that endogenous mal-spliced RNA from a tumor cell can stimulate the immune system even without therapeutic treatment.
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