Initial Myeloid Cell Status Is Associated with Clinical Outcomes of Renal Cell Carcinoma.
Saima SabrinaYuji TakedaTomoyuki KatoSei NaitoHiromi ItoYuki TakaiMasaki UshijimaTakafumi NarisawaHidenori KannoToshihiko SakuraiShinichi SaitohAkemi ArakiNorihiko TsuchiyaHironobu AsaoPublished in: Biomedicines (2023)
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-β1 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.
Keyphrases
- peripheral blood
- induced apoptosis
- dendritic cells
- transforming growth factor
- renal cell carcinoma
- acute myeloid leukemia
- cell therapy
- single cell
- epithelial mesenchymal transition
- flow cytometry
- long non coding rna
- poor prognosis
- mesenchymal stem cells
- cell cycle arrest
- protein protein
- small molecule
- high resolution
- single molecule