FLT3 ligand administration after hematopoietic cell transplantation increases circulating dendritic cell precursors that can be activated by CpG oligodeoxynucleotides to enhance T-cell and natural killer cell function

Biol Blood Marrow Transplant. 2005 Jan;11(1):23-34. doi: 10.1016/j.bbmt.2004.08.004.


Dendritic cells (DCs) are key effectors in innate immunity and play critical roles in triggering adaptive immune responses. FLT3 ligand (FLT3-L) is essential for DC development from hematopoietic progenitors. In a phase I clinical trial, we demonstrated that immunotherapy with subcutaneous injection of FLT3-L is safe and well tolerated in cancer patients recovering from autologous hematopoietic cell transplantation (HCT). FLT3-L administration significantly increased the frequency and absolute number of blood DC precursors without affecting other mature cell lineages during the 6-week course of FLT3-L therapy. After 14 days of FLT3-L administration, the number of blood CD11c + DCs, plasmacytoid DCs (PDCs), and CD14 + monocytes increased by 5.3-, 2.9-, 3.8-fold, respectively, and was maintained at increased levels throughout FLT3-L therapy. FLT3-L-increased blood DCs in HCT patients were immature and had modest enhancing effects on in vitro T-cell proliferation to antigens and natural killer (NK) cell function. The addition of type B CpG oligodeoxynucleotides (ODNs) to peripheral blood mononuclear cells obtained from HCT patients receiving FLT3-L therapy induced rapid maturation of both CD11c + DCs and PDCs and enhanced T-cell proliferative responses. In addition, CpG ODN induced potent activation of NK cells from FLT3-L-treated patients with increased surface CD69 expression and augmented cytotoxicity. CpG ODN-induced activation of NK cells was primarily via an indirect mechanism through PDCs. These findings suggest that FLT3-L mobilization of DC precursors followed by a specific DC stimulus such as CpG ODN may provide a novel strategy to manipulate antitumor immunity in patients after HCT.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antigen Presentation
  • Blood Cell Count
  • Breast Neoplasms / immunology
  • Breast Neoplasms / therapy
  • Cell Differentiation / drug effects
  • CpG Islands
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects*
  • Dendritic Cells / physiology
  • Female
  • Flow Cytometry
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Immunity / drug effects
  • Killer Cells, Natural / drug effects*
  • Killer Cells, Natural / physiology
  • Lymphocyte Activation
  • Lymphoma / immunology
  • Lymphoma / therapy
  • Male
  • Membrane Proteins / administration & dosage*
  • Membrane Proteins / pharmacology
  • Middle Aged
  • Oligodeoxyribonucleotides / pharmacology*
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / physiology


  • Membrane Proteins
  • Oligodeoxyribonucleotides
  • flt3 ligand protein