Pattern of glycosylphosphatidylinositol-anchored 80 kD protein (GPI-80) expression in peripheral blood as a marker for myeloid-derived suppressor cells (MDSCs) in metastatic renal cell cancer (mRCC) patients.

Abstract

504 Background: Metastatic renal cell cancer (mRCC) patients are afflicted with the immunosuppressed condition, and myeloid-derived suppressor cells (MDSCs) are considered to be associated with this condition. MDSCs are difficult to detect in peripheral blood as their cell structures are not uniform, resembling both neutrophils and monocytes. GPI-80 is known as a regulator of Mac-1 (CD11b/CD18) and closely related with neutrophilic maturation. In this study, we investigated whether the pattern of GPI-80 expression could serve as a useful marker for the detection of MDSCs in peripheral blood among mRCC patients. Methods: This study was approved by the Ethics Committee of Yamagata University’s Faculty of Medicine. Peripheral blood samples, collected from 12 mRCC patients before treatment and 12 healthy volunteers, were stained with several differentiation markers such as CD11b, CD16, CD15, CD33, and GPI-80. The samples were examined using flow cytometry to detect unusual differentiation of myeloid cells. To investigate the immunosuppressive function of GPI-80 positive cells, reactive oxygen species (ROS) was measured, and T cell proliferation assay was performed. Results: The coefficient of variation (CV) of GPI-80 was significantly augmented in the CD16hi neutrophil cell population (p = 0.0001). The mean fluorescence intensity (MFI) of GPI-80 was significantly increased in the CD33hi monocyte cell population (p = 0.0074) in the peripheral blood cells of mRCC patients. Furthermore, the GPI-80 CV in the CD16hi population was inversely correlated with the proliferative ability of T cells (p = 0.0214), and the GPI-80 MFI of the CD33hi population was correlated with ROS production (p = 0.0497). Conclusions: These results showed that the pattern of GPI-80 expression in peripheral blood cells is a simple and useful marker for unusual differentiation, which is linked to MDSC functions among mRCC patients. Further studies are, however, required to identify the role of GPI-80 as a prognostic or predictive marker in such patients.