ecDNA Formation

Extrachromosomal DNA (ecDNA), a circular, tumor-specific genetic material, in the progression and heterogeneity of cancer is becoming increasingly well recognized. While not much is known about the mechanisms behind immune evasion in cancers, ecDNA has been identified as a potential catalyst. ecDNA modifies normal gene regulation through novel enhancer interactions, increases chromatin availability, and promotes oncogene amplification. Its acentricity causes unequal segregation during cell division, which promotes rapid genome adaptation and evolution. Immunodepleted microenvironments, which are characterized by decreased cytotoxic T-cell activity, decreased immune cell infiltration, and decreased expression of MHC class I and II antigen presentation genes, are frequently observed in tumors that contain ecDNA. These cancers have identical tumor mutational impact and neoantigen load to ecDNA-negative tumors, indicating that immune evasion is caused by poor immune recognition rather than decreased immunogenicity. Treatment resistance and poor prognosis are also influenced by the dynamic activity of ecDNA, which includes its ability to reach and exit the genome. This chapter examines ecDNA as a significant tumor-intrinsic mechanism that facilitates immune escape and highlights its potential as a therapeutic target to enhance the effectiveness of cancer treatment.