title: The pattern of GPI-80 expression is a useful marker for unusual myeloid maturation in peripheral blood.
abstract: Myeloid-derived suppressor cells (MDSCs) have a wide spectrum of immunosuppressive activity; control of these cells is a new target for improving clinical outcomes in cancer patients. MDSCs originate from unusual differentiation of neutrophils or monocytes induced by inflammatory cytokines, including granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage (GM)-CSF. However, MDSCs are difficult to detect in neutrophil or monocyte populations because they are not uniform cells, resembling both neutrophils and monocytes; thus, they exist in a heterogeneous population. In this study, we investigated GPI-80, a known regulator of Mac-1 (CD11b/CD18) and associated closely with neutrophil maturation, to clarify this unusual differentiation. First, we demonstrated that the mean fluorescence intensity (MFI) of GPI-80 and coefficient of variation (CV) of GPI-80 were increased by treatment with G-CSF and GM-CSF, respectively, using a human promyelocytic leukaemia (HL60) cell differentiation model. To confirm the value of GPI-80 as a marker of unusual differentiation, we measured GPI-80 expression and MDSC functions using peripheral blood cells from metastatic renal cell carcinoma patients. The GPI-80 CV was augmented significantly in the CD16hineutrophil cell population, and GPI-80 MFI was increased significantly in the CD33himonocyte cell population. Furthermore, the GPI-80 CV in the CD16hipopulation was correlated inversely with the proliferative ability of T cells and the GPI-80 MFI of the CD33hipopulation was correlated with reactive oxygen species production. These results led us to propose that the pattern of GPI-80 expression in these populations is a simple and useful marker for unusual differentiation, which is related to MDSC functions.
authors: Department of Immunology, Yamagata University, Faculty of Medicine, Yamagata, Japan.
authors: Y
authors: Y
authors: Takeda
authors: Department of Urology, Yamagata University, Faculty of Medicine, Yamagata, Japan.
authors: T
authors: T
authors: Kato
authors: Department of Urology, Yamagata University, Faculty of Medicine, Yamagata, Japan.
authors: H
authors: H
authors: Ito
authors: Department of Urology, Yamagata University, Faculty of Medicine, Yamagata, Japan.
authors: Y
authors: Y
authors: Kurota
authors: Department of Urology, Yamagata University, Faculty of Medicine, Yamagata, Japan.
authors: A
authors: A
authors: Yamagishi
authors: Department of Urology, Yamagata University, Faculty of Medicine, Yamagata, Japan.
authors: T
authors: T
authors: Sakurai
authors: Department of Immunology, Yamagata University, Faculty of Medicine, Yamagata, Japan.
authors: A
authors: A
authors: Araki
authors: Department of Immunology, Yamagata University, Faculty of Medicine, Yamagata, Japan.
authors: H
authors: H
authors: Nara
authors: Department of Urology, Yamagata University, Faculty of Medicine, Yamagata, Japan.
authors: N
authors: N
authors: Tsuchiya
authors: Department of Immunology, Yamagata University, Faculty of Medicine, Yamagata, Japan.
authors: H
authors: H
authors: Asao
mesh_terms: D000328:Adult; D000368:Aged; D000581:Amidohydrolases / Q000235:genetics*; D015415:Biomarkers; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D015870:Gene Expression; D018922:HL-60 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; D016207:Cytokines; D058851:GPI-Linked Proteins; D017382:Reactive Oxygen Species; D000581:Amidohydrolases; C121771:VNN2 protein, human
keywords: GPI-80/VNN2; MDSCs; myeloid cell differentiation; renal cell carcinoma