Healthy myeloid-derived suppressor cells express the surface ectoenzyme Vanin-2 (VNN2)
David C Soler1, Amber Kerstetter-Fogle1, Andrew B Young2
1The Department of Neurosurgery, USA; The Brain Tumor and Neuro-Oncology Center, and the Center of Excellence for Translational Neuro-Oncology, USA; University Hospitals-Seidman Center and the Case Comprehensive Cancer Center, USA.
Molecular Immunology
|December 25, 2021
Summary
Researchers identified Vanin-2 (VNN2) as a novel positive cell-surface marker for human monocytic Myeloid-Derived Suppressor cells (Mo-MDSC) in healthy individuals. This discovery aids in Mo-MDSC identification and may assist in tumor diagnosis.
Area of Science:
- Immunology
- Cell Biology
- Biomarker Discovery
Background:
- Human monocytic Myeloid-Derived Suppressor cells (Mo-MDSC) are crucial immune regulators but lack definitive positive cell-surface markers, hindering their study.
- Accurate identification of Mo-MDSC is essential for understanding their role in immune suppression and disease.
Purpose of the Study:
- To identify novel positive cell-surface markers for human Mo-MDSC.
- To validate the utility of identified markers in distinguishing Mo-MDSC and assessing their functional properties.
- To explore the potential diagnostic value of these markers in cancer.
Main Methods:
- Microarray analysis was performed comparing Mo-MDSC from healthy subjects with CD14+ HLA-DRhigh monocytes.
- Vanin-2 (VNN2) protein expression was quantified on monocytes using flow cytometry.
- Functional assays assessed the T cell inhibitory capacity of VNN2-expressing monocytes.
Main Results:
- Vanin-2 (VNN2) was identified as a novel biomarker highly enriched in Mo-MDSC from healthy subjects (68% VNN2+ vs. 9% in CD14+ HLA-DRhigh monocytes).
- CD14+VNN2high monocytes exhibited a phenotype consistent with Mo-MDSC and suppressed CD8 T cell proliferation similarly to traditional Mo-MDSC.
- In glioma patients, VNN2 expression on CD14+ monocytes inversely correlated with tumor grade.
Conclusions:
- Vanin-2 (VNN2) serves as a reliable positive cell-surface marker for identifying Mo-MDSC in healthy individuals.
- CD14+VNN2high monocytes represent a Mo-MDSC-like population in healthy subjects, with potential diagnostic applications in oncology.
- The inverse correlation of VNN2 expression with glioma grade suggests its utility in tumor diagnosis.
