Related Experiment Video

Updated: May 9, 2025

Studying the Effects of Tumor-Secreted Paracrine Ligands on Macrophage Activation using Co-Culture with Permeable Membrane Supports
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Studying the Effects of Tumor-Secreted Paracrine Ligands on Macrophage Activation using Co-Culture with Permeable Membrane Supports

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Amplification of Extrachromosomal MYC Paralogs Shapes Immunosuppressive Tumor Microenvironment in Small Cell Lung

Jingwei Zhang1, Yueqi Jin2,3, Haodong Lin4

  • 1Department of Thoracic Surgery, Thoracic Oncology Institute, Peking University People's Hospital, Beijing, China.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|April 29, 2025
PubMed
Abstract

Insights

Extrachromosomal MYC-paralogs amplification in small cell lung cancer (SCLC) creates an immunosuppressive tumor microenvironment. This finding identifies a patient subgroup likely resistant to immunotherapy.

Area of Science:

  • Oncology
  • Cancer Genomics
  • Immunology

Background:

  • Immunotherapy shows promise in small cell lung cancer (SCLC), but limited patient benefits necessitate immunosuppressive biomarkers.
  • Extrachromosomal DNA (ecDNA) drives MYC-paralog amplification and cross-resistance in SCLC.

Purpose of the Study:

  • To investigate if ecDNA-mediated MYC-paralog amplification (ecMYC+) is associated with immunosuppressive features in SCLC.
  • To identify potential biomarkers for immunotherapy resistance in SCLC.

Main Methods:

  • Analysis of bulk RNA sequencing data from public databases and patient samples.
  • Immunohistochemistry and fluorescence in situ hybridization to detect MYC-paralog overexpression and amplification.
  • Imaging mass cytometry and multiplex immunohistochemistry to characterize the tumor immune microenvironment (TIME).

Main Results:

  • SCLC samples showed higher ecDNA copy numbers and ecMYC+ frequency compared to other cancer types.
  • ecMYC+ SCLC exhibited downregulated immune pathways and upregulated nucleotide metabolism.
  • ecMYC+ samples displayed increased MKI67, VEGFA, FAP, FOXP3 expression, reduced T cell infiltration, and altered immune cell spatial interactions.

Conclusions:

  • Extrachromosomal amplification of MYC-paralogs contributes to a suppressive TIME in SCLC.
  • ecMYC+ identifies a potential subgroup of SCLC patients resistant to immunotherapy.

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