EcDNA-driven oncogene super-expressors shape immunoevasive tumor microenvironment.

ABSTRACT: ecDNA contributes to cancer genetic heterogeneity through random segregation during mitosis. Emerging evidence links ecDNA to immune evasion, but the mechanism remains elusive. Using genetically engineered mouse models of pancreatic ductal adenocarcinoma (PDAC), we show that Kras and Myc oncogenes are amplified either on ecDNAs or as homogeneously staining regions (HSRs) on chromosomes. ecDNA-driven tumors are more aggressive in immunocompetent mice. Single-cell transcriptomic and histological analyses reveal that ecDNA-driven tumors rapidly establish an immunoevasive tumor microenvironment (TME), marked by increased myofibroblastic cancer-associated fibroblasts (myCAFs) and reduced T cell infiltration. Mechanistically, ecDNA heterogeneity generates a subset of cancer cells w

SUBMITTER: Qiao K 

PROVIDER: S-EPMC12642531 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature