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Repression of Multiple Myeloma Cell Growth In Vivo by Single-wall Carbon Nanotube SWCNT-delivered MALAT1 Antisense Oligos
Published on: December 13, 2018
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.
Abstract:
Cardiac myxoma (CM), a rare primary cardiac tumor, poses significant life-threatening risks. Current CM research has remained largely limited to clinical case observations and pathological analyses, thus restricting its clinical therapeutic impact. Fundamental research should be urgently strengthened to better support future CM treatment strategies. In this work, single-cell sequencing is used to elucidated the intricate cellular composition of the CM microenvironments. The mechanisms of heart myxoma cell growth are investigated via proteomics and organoid models, while our western blot analysis reveals cardiac myxoma's immune evasion strategies. This study successfully characterizes diverse cell types within the CM microenvironment. Notably, ap-CAF cells are found to effectively recruit immune cells via chemokine secretion, fostering immune microenvironment formation. The work's pseudotime trajectory analysis also demonstrates that CM tumor cells derive from mesenchymal stem cells. Additionally, this work demonstrated that the glycolysis pathway is significantly activated and fuels CM cell growth. Tumor cells exploit the SIRPα-CD47 immune checkpoint to evade the immune system by inhibiting antigen-presenting cell phagocytosis. Tumor-associated macrophages (TAMs) concurrently assume M2 polarization and suppress autoimmune activity through IL-10. This research comprehensively examines CM's microenvironmental cellular architecture, metabolic features, and immune escape mechanisms. These work's findings not only deepen the current understanding of CM's biological nature but also offer vital theoretical foundations for developing safer, more effective CM therapies.
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.

