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PD-L1 expression in multiple myeloma myeloid derived suppressor cells.

Laura G Rico1, Roser Salvia1, Jolene A Bradford2

  • 1Functional Cytomics Lab, Germans Trias i Pujol Research Institute (IGTP), ICO-Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Barcelona, Spain; Department of Cellular Biology, Physiology and Immunology, Autonomous University of Barcelona (UAB), Cerdanyola del Vallès, Spain.

Methods in Cell Biology
|April 3, 2025
PubMed
Summary

A new flow cytometry assay detects conformational changes in Programmed Cell Death Ligand 1 (PD-L1) on Myeloid-Derived Suppressor Cells in multiple myeloma. This method aids in classifying patients and studying immunotherapy drug interactions.

Keywords:
Checkpoint inhibitorsFlow cytometryImmunotherapyMultiple myelomaPDL1

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Area of Science:

  • Immunology
  • Oncology
  • Biotechnology

Background:

  • The Programmed Cell Death Protein 1/Programmed Cell Death Protein Ligand 1 (PD-1/PD-L1) axis is a key target in cancer immunotherapy.
  • PD-L1 is overexpressed in multiple myeloma (MM) but presents conformational challenges for antibody recognition on Myeloid-Derived Suppressor Cells (MDSCs).

Purpose of the Study:

  • To develop a flow cytometry assay for detecting PD-L1 conformational changes on MDSCs in MM.
  • To enable patient classification based on PD-L1 expression and study immunotherapy interactions.

Main Methods:

  • Development of a flow cytometry screening assay with minimal sample manipulation to preserve PD-L1 structure.
  • Assessment of PD-L1 levels in MDSCs from MM patients, with and without stimulation (PMA).
  • Kinetic analysis of PD-L1 expression and competitive binding experiments with durvalumab.

Main Results:

  • The assay successfully detected conformational changes in PD-L1 on MDSCs after stimulation.
  • MM patients could be classified based on differential PD-L1 detection post-stimulation.
  • Protocols for assessing PD-L1 kinetics, subcellular localization, and drug interactions were established.

Conclusions:

  • The developed flow cytometry assay is effective for assessing PD-L1 conformational changes in MDSCs.
  • This method offers a novel approach for MM patient stratification and evaluating PD-1/PD-L1 targeted therapies.
  • The assay platform has potential applications for studying conformational changes in other proteins.