Harnessing Viral Mimicry in Cancer Vaccines

Despite advances in mRNA-based cancer vaccines, therapeutic responses remain limited by poorly immunogenic tumors that fail to support effective T cell infiltration, expansion, and function. Epigenetic therapies can enhance tumor immunogenicity by reactivating transposable elements (TEs), triggering innate sensing of immunogenic nucleic acids through a process known as viral mimicry. In this seminar, I will discuss how the DNA methyltransferase inhibitors induces viral mimicry in preclinical tumour models, leading to type I interferon responses, enhanced antigen presentation, and remodeling of the immunosuppressive tumor microenvironment. This response depends on cancer-intrinsic nucleic acid sensors and supports the expansion and function of vaccine antigen-specific T cells within tumors. Together, these findings identify viral mimicry as a strategy to license therapeutic cancer vaccination and improve anti-tumor immunity.