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Microsatellite instability and PD-L1 expression in sarcomas: current evidence and clinical perspectives

  • 0Group of Experimental Biotherapy and Diagnostics, Institute for Regenerative Medicine, I.M. Sechenov First Moscow State Medical University, 119991, Moscow, Russia.
Medical Oncology +

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September 17, 2025

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September 17, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Microsatellite instability (MSI) and programmed death-ligand 1 (PD-L1) are rare but therapeutically relevant biomarkers in sarcomas. Assessing MSI, PD-L1, and lymphovascular invasion (LVI) may guide personalized immunotherapy for sarcoma patients.

Area Of Science

  • Oncology
  • Immunology
  • Biomarker Research

Background

  • Sarcomas are complex cancers with limited treatment options.
  • Biomarkers like Microsatellite Instability (MSI) and Programmed Death-Ligand 1 (PD-L1) are underexplored in sarcomas.
  • Lymphovascular Invasion (LVI) may influence immune response in sarcomas.

Purpose Of The Study

  • To analyze the incidence, clinical relevance, and immunotherapy implications of MSI and PD-L1 in sarcomas.
  • To explore the role of LVI in modulating sarcoma immune response.
  • To propose a framework for sarcoma diagnostics and treatment using these biomarkers.

Main Methods

  • Comprehensive literature review of MSI and PD-L1 in sarcoma.
  • Analysis of immunohistochemistry (IHC) and next-generation sequencing (NGS) data.
  • Review of recent clinical trials in sarcoma immunotherapy.

Main Results

  • MSI-high (MSI-H) sarcomas are rare but correlate with higher tumor mutational burden (TMB) and neoantigen load, suggesting checkpoint blockade sensitivity.
  • Concurrent MSI and PD-L1 expression, found in ~2-5% of sarcomas, may identify an immunogenic subgroup for personalized immunotherapy.
  • LVI-positive sarcomas might upregulate PD-L1 as an immune escape mechanism.

Conclusions

  • Dual assessment of MSI and PD-L1, alongside LVI status, is crucial for improving sarcoma prognostication and guiding immunotherapy.
  • A proposed framework incorporating MSI, IHC, PD-L1, and LVI can enhance precision oncology in sarcoma care.
  • Further translational research is needed to leverage these biomarkers for improved sarcoma treatment outcomes.

Keywords: