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

Antigen-presenting cells (APCs) are essential for stimulating antigen-speci fic 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-present ing activity of CD14(+) cells in vivo. Patients with metastatic solid malig nancies were treated with daily s.c. injections of either GM-CSF alone (2.5 mu g/kg/day) or GM-CSF in combination with IL-4 (0.5-6.0 mu g/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 endocyt otic activity, and the ability to stimulate T cells in a mixed leukocyte re action. Combination therapy also induced a dose-dependent increase in the n umber of CD14(-)/CD83(+) cells with APC activity. Clinically significant an d 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.