Granulocyte Macrophage Colony-stimulating Factor and Interleukin 4 Enhance the Number and Antigen-presenting Activity of Circulating CD 14 1 and CD 83 1 Cells in Cancer Patients 1
Antigen-presenting cells (APCs) are essential for stimulating antigenspecific immunity, including immunity against tumor cells. We hypothesized that systemic administration of granulocyte macrophage colonystimulating factor (GM-CSF) and interleukin (IL)-4, which promote monocytes to differentiate into dendritic cellsin 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 (2.5mg/kg/day) or GM-CSF in combination with IL-4 (0.5–6.0 mg/kg/day) in a multicohort study. When given alone, GMCSF increased the number of CD14 1 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.