Antitumor response of CD14+/CD16+ monocyte subpopulation

Exp Hematol. 2004 Aug;32(8):748-55. doi: 10.1016/j.exphem.2004.05.027.


Objective: Two main subpopulations of human blood monocytes are distinguished on the basis of CD14 and CD16 expression: the major population with enhanced expression of CD14 (CD14++ monocytes) and the minor one with a weak expression of CD14 coexpressing CD16 (CD14+/CD16+ monocytes). As monocytes and macrophages are involved in antitumor response of the host, we assessed the ability of CD14+/CD16+ monocytes to produce cytokines (intracellular expression, release) and reactive oxygen and nitrogen (ROI, RNI) intermediates following stimulation in vitro with tumor cells.

Materials and methods: Monocytes were isolated by elutriation and their subpopulations by FACS sorting. Monocytes and their subpopulations were cocultured with tumor cells. Cytokine (TNF-alpha, IL-12, and IL-10) production was assessed by determination of intracellular protein expression by flow cytometry, and release by ELISA. ROI induction was detected by chemiluminescence and O2- production by flow cytometry, whereas RNI by intracellular expression of inducible NO synthase (iNOS) and nitric oxide (NO) release assessed colorimetrically.

Results: CD14+/CD16+ monocytes stimulated with tumor cells showed significantly enhanced production of TNF-alpha, IL-12p40, IL-12p70 (intracellular expression, release), whereas little IL-10 release was observed. CD14+/CD16+ subpopulation did not produce ROI, but showed an increased iNOS expression and NO release. CD14+/CD16+ monocytes also exhibited enhanced cytotoxic and cytostatic activities against tumor cells.

Conclusions: CD14+/CD16+ cells constitute the main subpopulation of blood monocytes involved in antitumor response as judged by enhanced production of proinflammatory cytokines, RNI, and increased cytotoxic/cytostatic activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cytokines / biosynthesis
  • Cytotoxicity, Immunologic*
  • Humans
  • Lipopolysaccharide Receptors / analysis*
  • Monocytes / immunology*
  • Nitric Oxide / biosynthesis
  • Reactive Nitrogen Species
  • Reactive Oxygen Species
  • Receptors, IgG / analysis*


  • Cytokines
  • Lipopolysaccharide Receptors
  • Reactive Nitrogen Species
  • Reactive Oxygen Species
  • Receptors, IgG
  • Nitric Oxide