Increased presence of CD34+ cells in the peripheral blood of head and neck cancer patients and their differentiation into dendritic cells

Int J Cancer. 1997 Nov 27;73(5):663-9. doi: 10.1002/(sici)1097-0215(19971127)73:5<663::aid-ijc9>3.0.co;2-v.

Abstract

Patients with head and neck squamous cell carcinoma (HNSCC) have profound immune deficiencies. In 65% of these patients, there is an increased intra-tumoral presence of immune-suppressive CD34+ progenitor cells. The goal of the present study was to determine whether CD34+ cell levels were also increased in the peripheral blood of HNSCC patients and if these immune-suppressive cells could be differentiated into dendritic cells. Our results showed that CD34+ cell levels are increased in the peripheral blood of HNSCC patients. To assess if these CD34+ cells could differentiate into dendritic cells, they were isolated from the blood of HNSCC patients and cultured for 12 days with various cytokine combinations. Culturing CD34+ cells with stem cell factor (c-kit ligand) plus granulocyte-macrophage colony-stimulating factor resulted in the appearance of a significant proportion of cells expressing phenotypic markers characteristic of dendritic cells. Also, including tumor necrosis factor-alpha yielded a significant proportion of cells resembling the bipotential precursor cells for dendritic cells and monocytes (CD14+CD1a+), in addition to the dendritic-like cells. When the differentiation inducer 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] was added along with the cytokine combinations, the yield of cells having characteristics of dendritic cells was further increased. Cells that were derived from CD34+ cell cultures containing 1,25(OH)2D3 had a more potent capacity to present the recall antigen tetanus toxoid to autologous peripheral blood leukocytes and to stimulate a mixed leukocyte response compared to cultures to which 1,25(OH)2D3 had not been added. Our results show that CD34+ cells, whose frequency is increased in HNSCC patients, can be differentiated into cells that phenotypically and functionally resemble dendritic cells and that 1,25(OH)2D3 accentuates this differentiation.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigen Presentation
  • Antigens, CD34 / immunology*
  • Carcinoma, Squamous Cell / immunology
  • Carcinoma, Squamous Cell / pathology*
  • Cell Differentiation* / drug effects
  • Cells, Cultured
  • Cholecalciferol / pharmacology
  • Dendritic Cells / pathology*
  • Flow Cytometry
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Head and Neck Neoplasms / immunology
  • Head and Neck Neoplasms / pathology*
  • Humans
  • Leukocytes, Mononuclear / immunology
  • Lymphocyte Count
  • Recombinant Proteins
  • Stem Cell Factor / pharmacology
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / pathology*

Substances

  • Antigens, CD34
  • Recombinant Proteins
  • Stem Cell Factor
  • Cholecalciferol
  • Granulocyte-Macrophage Colony-Stimulating Factor