CD66b + monocytes represent a proinflammatory myeloid subpopulation in cancer

Cancer Immunol Immunother. 2021 Jan;70(1):75-87. doi: 10.1007/s00262-020-02656-y. Epub 2020 Jul 6.

Abstract

Myeloid-derived suppressor cells (MDSC) populate the peripheral blood and contribute to immune regulation in cancer. However, there is limited knowledge on the myeloid cell types with proinflammatory capacities that may serve as opponents of MDSC. In the circulation of cancer patients, a monocyte subpopulation was identified with a specific immunophenotype and transcriptomic signature. They were predominantly CD14+CD33hiCD16-/+HLA-DR+/hi cells that typically expressed CD66b. In accordance with the transcriptomics data, NALP3, LOX-1 and PAI-1 levels were also significantly upregulated. The CD66b+ monocytes displayed high phagocytic activity, matrix adhesion and migration, and provided costimulation for T cell proliferation and IFN-γ secretion; thus, they did not suppress T cell responses. Irrespective of clinical stage, they were identified in various cancers. In conclusion, the CD66b+ monocytes represent a novel myeloid subpopulation which is devoid of immune regulatory influences of cancer and displays enhanced proinflammatory capacities.

Keywords: Monocyte; Monocyte subtypes; Myeloid-derived suppressor cells (MDSC); Neutrophil; PMN-MDSC; Transcriptomics.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / immunology*
  • Cell Adhesion Molecules / immunology*
  • Cell Movement / immunology
  • Cell Proliferation / physiology
  • Female
  • GPI-Linked Proteins / immunology
  • HLA-DR Antigens / immunology
  • Humans
  • Immunophenotyping / methods
  • Inflammation / immunology*
  • Interferon-gamma / immunology
  • Male
  • Middle Aged
  • Monocytes / immunology*
  • Myeloid Cells / immunology*
  • NLR Family, Pyrin Domain-Containing 3 Protein / immunology
  • Neoplasms / immunology*
  • Plasminogen Activator Inhibitor 1 / immunology
  • Scavenger Receptors, Class E / immunology
  • T-Lymphocytes / immunology
  • Transcriptome / immunology
  • Up-Regulation / immunology

Substances

  • Antigens, CD
  • CEACAM8 protein, human
  • Cell Adhesion Molecules
  • GPI-Linked Proteins
  • HLA-DR Antigens
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Plasminogen Activator Inhibitor 1
  • Scavenger Receptors, Class E
  • Interferon-gamma