The 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.
The Department of Dermatology, University Hospitals-Cleveland Medical Center and the Case Western University School of Medicine, 11100 Euclid Avenue, Cleveland, OH, 44106, USA; The Murdough Family Center for Psoriasis, University Hospitals-Cleveland Medical Center and the Case Western University School of Medicine, 11100 Euclid Avenue, Cleveland, OH, 44106, USA.
Mol Immunol. 2022 Feb;142:1-10. doi: 10.1016/j.molimm.2021.12.011. Epub 2021 Dec 23.
Study of human monocytic Myeloid-Derived Suppressor cells Mo-MDSC (CD14 HLA-DR) 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-DR 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-DR 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. CD14VNN2 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. CD14VNN2 monocytes thus appear to mark a monocytic population similar to Mo-MDSC only in healthy subjects, which may be useful for tumor diagnoses.
人类单核细胞来源的髓系抑制细胞(Mo-MDSC,CD14 HLA-DR)的研究受到缺乏阳性细胞表面标志物的阻碍。为了鉴定 Mo-MDSC 的阳性标志物,我们进行了微阵列分析,比较了健康受试者与 CD14 HLA-DR 单核细胞的 Mo-MDSC 细胞。我们发现表面外切酶 Vanin-2(VNN2)蛋白在健康受试者 Mo-MDSC 中高度富集,是一种新型的生物标志物。事实上,健康受试者 Mo-MDSC 细胞表达 68%的 VNN2,而 CD14 HLA-DR 细胞仅表达 9%的 VNN2(n = 4,p < 0.01)。前 10%阳性的 VNN2 单核细胞表达 CD33 和 CD11b,而 HLA-DR、CD3、CD15、CD19 和 CD56 阴性,符合 Mo-MDSC 表型。CD14VNN2 单核细胞能够抑制 CD8 T 细胞增殖,与传统的 Mo-MDSC 相比分别为 51%和 48%。然而,来自脑肿瘤患者的 CD14VNN2 单核细胞的表达与其分级呈负相关。因此,CD14VNN2 单核细胞似乎仅在健康受试者中标记类似于 Mo-MDSC 的单核细胞群体,这可能对肿瘤诊断有用。