Granulocyte macrophage colony-stimulating factor and interleukin 4 enhance the number and antigen-presenting activity of circulating CD14+ and CD83+ cells in cancer patients

Cancer Res. 2000 Apr 1;60(7):1934-41.


Antigen-presenting cells (APCs) are essential for stimulating antigen-specific immunity, including immunity against tumor cells. We hypothesized that systemic administration of granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4, which promote monocytes to differentiate into dendritic cells in vitro, might enhance the number and antigen-presenting activity of CD14+ cells in vivo. Patients with metastatic solid malignancies were treated with daily s.c. injections of either GM-CSF alone (2.5 microg/kg/day) or GM-CSF in combination with IL-4 (0.5-6.0 microg/kg/day) in a multicohort study. When given alone, GM-CSF increased the number of CD14+ cells but did not enhance the cells' expression of APC markers or antigen-presenting activity. In contrast, combination therapy with GM-CSF and IL-4 stimulated CD14+ cells to acquire several APC characteristics including increased expression of HLA-DR and CD11c, decreased CD14, increased endocytotic activity, and the ability to stimulate T cells in a mixed leukocyte reaction. Combination therapy also induced a dose-dependent increase in the number of CD14-/CD83+ cells with APC activity. Clinically significant and sustained tumor regression was observed in one patient. Systemic therapy with GM-CSF and IL-4 may provide a mechanism for increasing the number and function of APCs in patients with cancer.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen-Presenting Cells / drug effects
  • Antigen-Presenting Cells / immunology*
  • Antigens, CD / blood
  • CD18 Antigens / blood*
  • Dose-Response Relationship, Drug
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage
  • Granulocyte-Macrophage Colony-Stimulating Factor / adverse effects*
  • Humans
  • Interleukin-4 / administration & dosage
  • Interleukin-4 / adverse effects*
  • Lipopolysaccharide Receptors / blood*
  • Lymphocytes / immunology*
  • Neoplasms / blood
  • Neoplasms / drug therapy*
  • Neoplasms / immunology*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects


  • Antigens, CD
  • CD18 Antigens
  • Lipopolysaccharide Receptors
  • Recombinant Proteins
  • Interleukin-4
  • Granulocyte-Macrophage Colony-Stimulating Factor