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Updated: May 26, 2026

Modeling Osteosarcoma Using Li-Fraumeni Syndrome Patient-derived Induced Pluripotent Stem Cells
Published on: June 13, 2018
PSIP1 Orchestrates Immune Escape in Osteosarcoma: Insights From Single-Cell Analysis and Implications for
Simin Liu1, Hong Yan1, Wei Ku1
1Department of Spinal Surgery, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, Hubei, China.
Background:
Osteosarcoma (OS) is characterized by a highly heterogeneous tumor microenvironment (TME) that frequently limits the efficacy of immunotherapy. Identifying molecular drivers of immune escape (IE) is essential for improving therapeutic outcomes.
Methods:
We integrated single-cell RNA sequencing (scRNA-seq) and bulk transcriptomic data to dissect the OS immune landscape. Utilizing high-dimensional weighted gene coexpression network analysis (hdWGCNA), we identified gene modules specifically associated with IE.
Results:
Within the IE-related module, PSIP1 emerged as the most significant prognostic hub gene. ScRNA-seq analysis localized PSIP1 primarily to malignant cell populations. High PSIP1 expression consistently correlated with abbreviated overall survival across multiple independent cohorts. Functional enrichment and GSEA revealed that PSIP1 is intrinsically linked to the suppression of critical immune effectors, including B-cell signaling, lymphocyte chemotaxis, and NK cell-mediated cytotoxicity. Crucially, PSIP1 exhibited robust predictive performance for immunotherapy response; elevated PSIP1 levels were associated with diminished activity of multiple established immune-response signatures and poor survival in patients undergoing checkpoint blockade.
Conclusion:
Our study positions PSIP1 as a novel orchestrator of immune evasion and a promising predictive biomarker for immunotherapy resistance in OS, offering a potential target to overcome therapeutic recalcitrance.
Insights
This study identifies PSIP1 as a key driver of immune escape in osteosarcoma (OS). High PSIP1 expression predicts poor immunotherapy response and survival, highlighting its potential as a therapeutic target.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Osteosarcoma (OS) features a complex tumor microenvironment (TME) that often hinders immunotherapy effectiveness.
- Identifying molecular mechanisms of immune escape (IE) is critical for enhancing treatment outcomes in OS.
Purpose of the Study:
- To investigate the molecular drivers of immune escape in the OS tumor microenvironment.
- To identify potential biomarkers for predicting immunotherapy response in osteosarcoma.
Main Methods:
- Integrated single-cell RNA sequencing (scRNA-seq) and bulk transcriptomic data.
- Applied high-dimensional weighted gene coexpression network analysis (hdWGCNA) to identify IE-associated gene modules.
- Utilized functional enrichment and Gene Set Enrichment Analysis (GSEA).
Main Results:
- PSIP1 was identified as a significant prognostic hub gene within IE-related modules, predominantly expressed in malignant cells.
- High PSIP1 expression correlated with reduced overall survival across multiple patient cohorts.
- PSIP1 was linked to suppressed immune effector functions (B-cell signaling, lymphocyte chemotaxis, NK cell cytotoxicity) and predicted poor response to checkpoint blockade immunotherapy.
Conclusions:
- PSIP1 is a novel orchestrator of immune evasion in osteosarcoma.
- PSIP1 serves as a promising predictive biomarker for immunotherapy resistance in OS.
- Targeting PSIP1 may offer a strategy to overcome therapeutic resistance in osteosarcoma.
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