4.5 Article

Healthy myeloid-derived suppressor cells express the surface ectoenzyme Vanin-2 (VNN2)

Journal

MOLECULAR IMMUNOLOGY
Volume 142, Issue -, Pages 1-10

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2021.12.011

Keywords

Immunosuppression; Mo-MDSC; VNN2; GPI-80

Funding

  1. Peter D. Cristal Foundation [R01AR051498, P30AR039750]
  2. Peter D. Cristal Foundation
  3. UH Center of Excellence in Translational Neuro-Oncology (CETNO)
  4. Kimble Family Foundation
  5. Ferry Family Foundation

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This study focused on human monocytic Myeloid-Derived Suppressor cells (Mo-MDSC) and identified Vanin-2 protein as a novel biomarker highly enriched in healthy individuals, but with an inverse correlation to grade in glioma patients. CD14(+)VNN2(high) monocytes may mark a monocytic population similar to Mo-MDSC only in healthy subjects, which could be useful for tumor diagnoses.
Study of human monocytic Myeloid-Derived Suppressor cells Mo-MDSC (CD14(+) HLA-DRneg/low) has been hampered by the lack of positive cell-surface markers. In order to identify positive markers for Mo-MDSC, we performed microarray analysis comparing Mo-MDSC cells from healthy subjects versus CD14(+) HLA-DRhigh monocytes. We have identified the surface ectoenzyme Vanin-2(VNN2) protein as a novel biomarker highly-enriched in healthy subjects Mo-MDSC. Indeed, healthy subjects Mo-MDSC cells expressed 68 % VNN2, whereas only 9% VNN2 expression was observed on CD14(+) HLA-DRhigh cells (n = 4 p < 0.01). The top 10 percent positive VNN2 monocytes expressed CD33 and CD11b while being negative for HLA-DR, CD3, CD15, CD19 and CD56, consistent with a Mo-MDSC phenotype. CD14(+)VNN2(high) monocytes were able to inhibit CD8 T cell proliferation comparably to traditional Mo-MDSC at 51 % and 48 % respectively. However, VNN2 expression on CD14(+) monocytes from glioma patients was inversely correlated to their grade. CD14(+)VNN2(high) monocytes thus appear to mark a monocytic population similar to Mo-MDSC only in healthy subjects, which may be useful for tumor diagnoses.

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