The pattern of GPI‐80 expression is a useful marker for unusual myeloid maturation in peripheral blood

Summary

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 CD16 ^hi neutrophil cell population, and GPI‐80 MFI was increased significantly in the CD33 ^hi monocyte cell population. Furthermore, the GPI‐80 CV in the CD16 ^hi population was correlated inversely with the proliferative ability of T cells and the GPI‐80 MFI of the CD33 ^hi population 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.