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

The therapeutic outcome of immune checkpoint inhibition (ICI) can be improved through combination treatments with ICI therapy. Myeloid-derived suppressor cells (MDSCs) strongly suppress tumor immunity. MDSCs are a heterogeneous cell population, originating from the unusual differentiation of neutrophils/monocytes induced by environmental factors such as inflammation. The myeloid cell population consists of an indistinguishable mixture of various types of MDSCs and activated neutrophils/monocytes. In this study, we investigated whether the clinical outcomes of ICI therapy could be predicted by estimating the status of the myeloid cells, including MDSCs. Several MDSC indexes, such as glycosylphosphatidylinositol-anchored 80 kD protein (GPI-80), CD16, and latency-associated peptide-1 (LAP-1; transforming growth factor- fi1 precursor), were analyzed via flow cytometry using peripheral blood derived from patients with advanced renal cell carcinoma (n = 51) immediately before and during the therapy. Elevated CD16 and LAP-1 expressions after the first treatment were associated with a poor response to ICI therapy. Immediately before ICI therapy, GPI-80 expression in neutrophils was significantly higher in patients with a complete response than in those with disease progression. This is the first study to demonstrate a relationship between the status of the myeloid cells during the initial phase of ICI therapy and clinical outcomes.

Automated summary

The combination of immune checkpoint inhibition (ICI) therapy with other treatments can improve therapeutic outcomes. In this study, the expression of various myeloid-derived suppressor cells (MDSCs) markers, such as GPI-80, CD16, and LAP-1, were analyzed before and during ICI therapy in 51 patients with advanced renal cell carcinoma. It was found that elevated CD16 and LAP-1 expressions after treatment were associated with a poor response to ICI therapy, while higher GPI-80 expression in neutrophils before therapy was correlated with a complete response.