Related Experiment Video

Updated: Jan 10, 2026

In Vivo Immunogenicity Screening of Tumor-Derived Extracellular Vesicles by Flow Cytometry of Splenic T Cells
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In Vivo Immunogenicity Screening of Tumor-Derived Extracellular Vesicles by Flow Cytometry of Splenic T Cells

Published on: September 23, 2021

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ecDNA-driven oncogene super-expressors shape immunoevasive tumor microenvironment

Kailiang Qiao1, Qing-Lin Yang1,2, Tuo Li2,3,4

  • 1Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Biorxiv : the Preprint Server for Biology
|November 26, 2025
PubMed

Insights

Extrachromosomal DNA (ecDNA) drives pancreatic cancer aggression and immune evasion by creating "super-expressor" cells. These cells remodel the tumor microenvironment, reducing T cell infiltration and promoting cancer growth.

Area of Science:

  • Oncology
  • Cancer Genetics
  • Immunology

Background:

  • Extrachromosomal DNA (ecDNA) contributes to cancer genetic heterogeneity.
  • Emerging evidence suggests a link between ecDNA and immune evasion, but the underlying mechanisms are not fully understood.

Purpose of the Study:

  • To investigate the role of ecDNA in pancreatic ductal adenocarcinoma (PDAC) progression and immune evasion.
  • To elucidate the mechanism by which ecDNA influences the tumor microenvironment (TME) and anti-tumor immunity.

Main Methods:

  • Genetically engineered mouse models of PDAC.
  • Single-cell transcriptomic and histological analyses.
  • Analysis of TME components, including cancer-associated fibroblasts (CAFs) and T cells.

Main Results:

  • ecDNA-driven tumors, characterized by amplified Kras and Myc oncogenes, exhibit increased aggressiveness in immunocompetent mice.
  • ecDNA promotes rapid establishment of an immunoevasive TME with increased myofibroblastic CAFs (myCAFs) and reduced T cell infiltration.
  • A subset of cancer cells, termed "super-expressors," exhibit extremely high Kras expression, secrete amphiregulin, promote myCAF expansion, and suppress T cell infiltration.

Conclusions:

  • ecDNA plays a causal role in remodeling the TME, contributing to pancreatic cancer heterogeneity and immune evasion.
  • Super-expressor cells driven by ecDNA establish an immunoevasive niche in PDAC.
  • Targeting ecDNA or its downstream effectors may represent a novel therapeutic strategy for PDAC.

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