Aberrant Phenotype and Function of Dendritic Cells in Adult B Lineage Acute Lymphoblastic Leukemia

Immunol Invest. 2019 Nov;48(8):781-793. doi: 10.1080/08820139.2019.1610428. Epub 2019 May 7.

Abstract

Dendritic cells (DCs) play a major role in regulating immune responses, but the aberrant phenotype and function of defective DCs in adult acute lymphoblastic leukemia (ALL) remain unclear. Here, B lineage ALL (B-ALL) patients were divided into groups according to different standards. By course of disease: newly diagnosed (ND), complete remission (CR), consolidation (CONS). By stratification: high risk (HR), standard risk (SR). By minimal residual disease (MRD): MRD positive(MRD+), MRD negative (MRD-). The proportion of plasmacytoid DC(pDC) and myeloid DC(mDC) were compared within these standards. The costimulatory molecule levels of pDC, mDC in ND and CR were measured and the function of peripheral blood monocyte-derived DC(MoDC)s were examined. We found proportions of pDC and mDC in ND were both lower compared to control group and gradually increased after CR. In HR and MRD+, the proportions were also lower compared to SR and MRD- at CR stage, respectively; but there were no difference between these comparisons when newly diagnosed. In ND, both CD80, CD86 levels in pDC, mDC were higher while the levels in activated MoDCs were lower when compared to control and CR group, respectively. The dextran uptake of MoDCs, T cell proliferation promoting ability, IL-12, BAFF, INF-α levels in supernatant and their mRNA relative expression in activated MoDCs in ND were also lower than those in control and CR group. So, DCs in B-ALL display suppressed status in phenotype and function,which would be gradually restored after effective chemotherapy. pDC and mDC could respond to patient condition, DCs proportion may be useful for monitoring disease progression.

Keywords: Dendritic cells; acute lymphoblastic leukemia; costimulatory molecules; minimal residual disease.

MeSH terms

  • Adult
  • B-Cell Activating Factor / genetics
  • B-Cell Activating Factor / immunology
  • B-Cell Activating Factor / metabolism
  • Cell Proliferation / genetics
  • Cells, Cultured
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Female
  • Gene Expression / immunology
  • Humans
  • Interferon-alpha / genetics
  • Interferon-alpha / immunology
  • Interferon-alpha / metabolism
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology*
  • Male
  • Middle Aged
  • Monocytes / immunology*
  • Monocytes / metabolism
  • Neoplasm, Residual / genetics
  • Neoplasm, Residual / immunology
  • Neoplasm, Residual / metabolism
  • Phenotype
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / immunology*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • Remission Induction

Substances

  • B-Cell Activating Factor
  • Interferon-alpha
  • TNFSF13B protein, human