A high number of PD-L1+ CD14+ monocytes in peripheral blood is correlated with shorter survival in patients receiving immune checkpoint inhibitors

Cancer Immunol Immunother. 2021 Feb;70(2):337-348. doi: 10.1007/s00262-020-02686-6. Epub 2020 Aug 5.

Abstract

Purpose: Targeting of anti-programmed cell death protein-1 (PD-1) and anti-programmed death-ligand 1 (PD-L1) is a standard therapeutic strategy for various cancers. The aim of the present study was to investigate the prognostic effect of pretreatment PD-L1 expression levels in peripheral blood mononuclear cell (PBMC) subsets for patients with several cancer types receiving anti-PD-1 blockade therapies.

Patients and methods: Thirty-two patients undergoing anti-PD-L1 blockade therapy, including 15 with non-small cell lung cancer, 14 with gastric cancer, 1 with melanoma, 1 with parotid cancer, and 1 with bladder cancer, were recruited for the present study. PD-L1 expression levels in CD3+, CD4+, CD8+, CD45RA+ and CCR7+ T cells; CD20+ B cells; CD14+ and CD16+ monocytes were measured via flow cytometry before treatment. The percentages of PD-L1+ cells in respective PBMC subsets were compared with respect to different clinicopathological conditions and the association with overall survival (OS) was assessed.

Results: The percentages of PD-L1+ with CD3+, CD4+ and CD8+ T cells including naïve and memory T cell subsets, or CD20+ B cells during pretreatment were not markedly correlated with the OS of patients (p > 0.05); however, the percentage of the PD-L1+ CD14+ monocyte subset was significantly correlated with OS (p = 0.0426).

Conclusion: Increase in pretreatment expression levels of PD-L1 on CD14+ monocytes is associated with the OS of patients treated with immune checkpoint inhibitors. Further evaluation of large sample size and each specific cancer type might clarify the predictive role of PBMC in patients.

Keywords: CD14; Nivolumab; Pembrolizumab; Prognosis; Programmed death-1; Programmed death-ligand 1.

MeSH terms

  • B7-H1 Antigen / adverse effects
  • B7-H1 Antigen / drug effects*
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / adverse effects*
  • Lipopolysaccharide Receptors / drug effects*
  • Male
  • Monocytes / metabolism*
  • Survival Analysis

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • Immune Checkpoint Inhibitors
  • Lipopolysaccharide Receptors