GPI-80 as a Useful Index for Myeloid Cell Heterogeneity and a Potential Prognostic Biomarker for Metastatic Renal Cell Carcinoma

Abstract

Myeloid-derived suppressor cells (MDSCs), which include neutrophilic MDSCs and monocytic MDSCs, exhibit high immunosuppressive activity. Glycosylphosphatidylinositol-anchored 80 kD protein (GPI-80) is selectively expressed on mature neutrophils in healthy individuals. Increased GPI-80 expression on monocytes and variations in GPI-80 expression on neutrophils indicate the appearance of MDSCs in the peripheral blood of cancer patients. However, it is still unclear whether GPI-80 expression on myeloid cells, neutrophilic MDSCs and monocytic MDSCs, is correlated with the clinical outcomes of patients with cancer. In this study, we investigated the characteristics of myeloid cells expressing GPI-80 and the implication of GPI-80 expression in the clinical outcomes of patients with metastatic renal cell carcinoma (mRCC), in which primary renal cell carcinoma spreads from the kidney to other organs. The study included 20 patients with mRCC (a mean age of 66.0 years) and 16 healthy volunteers (a mean age of 47.8 years). To determine the heterogeneity of myeloid cells in peripheral blood samples, we performed the threedimensional principal component analysis using the combination of GPI-80, CD16, and latency-associated peptide-1 (LAP), derived from the N-terminal region of transforming growth factor-β1 precursor. The results showed that myeloid cells in mRCC patients were widely distributed and clearly distinguishable from those in the healthy volunteers. The survival analysis revealed that GPI-80 expression on neutrophils and monocytes was correlated with poor prognostic outcomes of patients with mRCC. In conclusion, the expression of GPI-80 on myeloid cells, a useful index for the heterogeneity of MDSCs, serves as a potential prognostic biomarker for mRCC.

Initial Myeloid Cell Status Is Associated with Clinical Outcomes of Renal Cell Carcinoma

“…Notably, elevated GPI-80 expression has been reported in activated neutrophils [13]. We further demonstrated that increased expression of the coefficient of variation (CV) of GPI-80 (GPI-80 CV) on neutrophilic cells (CD16 hi cells) indicates unusual differentiation of neutrophils related to MDSC functions [10,12].…”

“…Previously, we demonstrated a method for the identification of myeloid cells from peripheral blood via staining with the myeloid cell marker CD33 and the neutrophil maturation marker CD16 (FcγRIII) in cases of RCC [9][10][11]. We revealed that the expression of CD16 and the TGFβ precursor molecule latency-associated peptide-1 (LAP-1) on monocytic cells (CD33 hi cells) is an indicator of MDSC status, as these parameters are involved in the suppression of antitumor immunity in patients with RCC [12]. Moreover, we identified that increased expression of glycosylphosphatidylinositol-anchored 80 kD protein (GPI-80) is an indicator of neutrophil maturation [10].…”

Five patterns of cell signaling pathways associated with cell behavior

“…The contraction and fluctuation of cell clusters are useful for categorizing the signal characteristics. Previously, we demonstrated that CV of the neutrophil surface molecule GPI-80 was useful for the detection of neutrophil differentiation and heterogeneity (Kato et al, 2019;Takeda et al, 2016). These observations suggest that the categorization will be not only used for phosphorylated molecules but also cell surface molecules.…”

Genomic and Transcriptomic Predictors of Response to Immune Checkpoint Inhibitors in Melanoma Patients: A Machine Learning Approach

“…While MDSCs are known to inhibit CD8+ T cell proliferation, this study described an inverse association between CD14+ monocytes expressing VNN2 and glioma patient’s tumor grade potentially highlighting a role for VNN2 in less aggressive tumors [ 49 ]. In another study on metastatic renal cell carcinoma, VNN2 expression on monocytes and neutrophils was found to be correlated with poor prognostic outcomes [ 50 ]. Considering the limited work pertaining to VNN2′s significance in melanoma, mechanistic studies describing its effect on the tumor immune microenvironment are needed to establish practical recommendations.…”