Malignant counterpart of myeloid dendritic cell (DC) belonging to acute myelogenous leukemia (AML) exhibits a dichotomous immunoregulatory potential

J Leukoc Biol. 2003 Jan;73(1):82-90. doi: 10.1189/jlb.0602267.

Abstract

Dendritic cells (DCs) play a central role in immune regulation. Some leukemic cells are argued to be malignant counterparts of DC because of their ability to differentiate into leukemic DC. We characterize DC-like leukemia homogenously expressing CD11c+CD86+ in acute myelogenous leukemia patients. They express the Wilms' tumor-1 antigen and common DC phenotypes (i.e., fascin+, CD83+, and DR+) directly. Purified leukemic cells produce interleukin-12 (IL-12) simultaneously with Fas ligand (FasL) and IL-6, which may suppress T cell-mediated immunity. These cells can elicit strong allogeneic T cell responses as well as induce tumor-specific CD8+ cytotoxic T cells, suggesting that they effectively present tumor-associated antigens. In contrast, they drive primary T cells toward apoptosis mediated in a tumor-specific way by a Fas-FasL interaction. Taken together, DC-like leukemia uniquely influences immune surveillance in contradictory ways, some of which may be involved in the mechanism of immune escape.

MeSH terms

  • Aged
  • Antigens, CD / analysis
  • Apoptosis
  • B7-2 Antigen
  • CD11c Antigen / analysis
  • Case-Control Studies
  • Cytotoxicity Tests, Immunologic
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Dendritic Cells / pathology*
  • Fas Ligand Protein
  • Female
  • Humans
  • Immunity, Cellular
  • Interleukin-12 / metabolism
  • Interleukin-6 / metabolism
  • Leukemia, Myeloid, Acute / immunology
  • Leukemia, Myeloid, Acute / pathology*
  • Male
  • Membrane Glycoproteins / analysis
  • Membrane Glycoproteins / physiology
  • Middle Aged
  • Monocytes / cytology
  • T-Lymphocytes / cytology
  • WT1 Proteins / analysis

Substances

  • Antigens, CD
  • B7-2 Antigen
  • CD11c Antigen
  • CD86 protein, human
  • FASLG protein, human
  • Fas Ligand Protein
  • Interleukin-6
  • Membrane Glycoproteins
  • WT1 Proteins
  • Interleukin-12