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

Abstract

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.

State-of-the-Art Cancer Biology, Biodiagnostics and Therapeutics in Japan

“…Next, Kawashita et al revealed that the degree of radiation-induced mucositis can be predicted on the basis of patient lymphocyte counts at the pre-radiation stage [5]. Other studies focusing on individual cancer types are included in this Special Edition, with research on breast cancer [6], renal cell carcinoma [7,8], ovarian cancer from ovarian endometrioma [9], and inflammatory bowel disease (IBD), conditions which sometimes transform into cancer-prone phenotype [10]. Breast cancer is the most commonly diagnosed cancer in women, and Uchida et al identified the nine candidate genes constituting therapeutic targets of breast cancer using existing databases.…”

“…Clear cell renal cell carcinoma (ccRCC) is dominant in kidney cancer, the mortality rate for which has recently increased worldwide. Sabrina et al demonstrated that the outcome is predictable by the status of the myeloid cells during immune checkpoint inhibition (ICI) therapy [7]. Kurota et al showed the implication of the expression of the hemoglobin beta-chain in the tissue [8].…”