Impaired antigen presentation and potent phagocytic activity identifying tumor-tolerant human monocytes

Biochem Biophys Res Commun. 2012 Jun 29;423(2):331-7. doi: 10.1016/j.bbrc.2012.05.124. Epub 2012 May 31.

Abstract

Monocyte exposure to tumor cells induces a transient state in which these cells are refractory to further exposure to cancer. This phenomenon, termed "tumor tolerance", is characterized by a decreased production of proinflammatory cytokines in response to tumors. In the past, we found that this effect comprises IRAK-M up regulation and TLR4 and CD44 activation. Herein we have established a human model of tumor tolerance and have observed a marked down-regulation of MHCII molecules as well as the MHCII master regulator, CIITA, in monocytes/macrophages. These cells combine an impaired capability for antigen presentation with potent phagocytic activity and exhibit an M2-like phenotype. In addition circulating monocytes isolated from Chronic Lymphocytic Leukemia patients exhibited the same profile as tumor tolerant cells after tumor ex vivo exposition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation*
  • HeLa Cells
  • Histocompatibility Antigens Class II / immunology
  • Humans
  • Immune Tolerance*
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology
  • Lipopolysaccharides / immunology
  • Macrophages / immunology
  • Models, Biological*
  • Monocytes / immunology*
  • Neoplasms / immunology*
  • Nuclear Proteins / immunology
  • Phagocytosis*
  • Trans-Activators / immunology

Substances

  • Histocompatibility Antigens Class II
  • Lipopolysaccharides
  • MHC class II transactivator protein
  • Nuclear Proteins
  • Trans-Activators