Single-cell RNA sequencing and proteomics uncover SIRPα-CD47 immune checkpoint and glycolysis-driven immune evasion

Xinyuan Zhu1,2,3, Qingle Gao2, Xintong Dai2

  • 1Department of Cardiovascular Surgery, The Fifth Central Hospital of Tianjin, Tianjin, China.

Frontiers in Immunology
|September 17, 2025
PubMed

Insights

Cardiac myxoma (CM) cells originate from mesenchymal stem cells and utilize the SIRPα-CD47 checkpoint for immune evasion. Glycolysis fuels CM growth, offering new therapeutic targets for this rare cardiac tumor.

Area of Science:

  • Oncology
  • Cardiology
  • Immunology

Background:

  • Cardiac myxoma (CM) is a rare primary cardiac tumor with limited research beyond clinical observations.
  • Existing research restricts the clinical therapeutic impact of CM.
  • Strengthening fundamental research is crucial for advancing CM treatment strategies.

Purpose of the Study:

  • To elucidate the cellular composition and microenvironment of cardiac myxoma.
  • To investigate the growth mechanisms and immune evasion strategies of CM.
  • To provide a foundation for developing novel CM therapies.

Main Methods:

  • Single-cell sequencing to characterize CM microenvironment.
  • Proteomics and organoid models to study CM cell growth mechanisms.
  • Western blot analysis for immune evasion strategies.

Main Results:

  • Diverse cell types within the CM microenvironment were identified, including ap-CAF cells recruiting immune cells.
  • CM tumor cells were shown to derive from mesenchymal stem cells.
  • Activated glycolysis fuels CM growth, and tumor cells use the SIRPα-CD47 checkpoint for immune evasion.
  • Tumor-associated macrophages (TAMs) exhibit M2 polarization, suppressing autoimmune activity via IL-10.

Conclusions:

  • This study provides a comprehensive analysis of CM's cellular architecture, metabolism, and immune escape mechanisms.
  • Findings deepen the understanding of CM's biological nature.
  • The research offers theoretical foundations for developing safer and more effective CM therapies.

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