Granulocyte macrophage colony-stimulating factor and interleukin 4 enhance the number and antigen-presenting activity of circulating CD14+ and CD83+ cells in cancer patients.
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.
Roth
M D
MD
Division of Pulmonary and Critical Care Medicine, Jonsson Comprehensive Cancer Center, University of California at Los Angeles School of Medicine, 90095-1690, USA. mroth@mednet.ucla.edu
Gitlitz
B J
BJ
Kiertscher
S M
SM
Park
A N
AN
Mendenhall
M
M
Moldawer
N
N
Figlin
R A
RA
D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology*; D015703:Antigens, CD / Q000097:blood; D018821:CD18 Antigens / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D015847:Interleukin-4 / Q000008:administration & dosage / Q000009:adverse effects*; D018950:Lipopolysaccharide Receptors / Q000097:blood*; D008214:Lymphocytes / Q000276:immunology*; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects
D015703:Antigens, CD; D018821:CD18 Antigens; D018950:Lipopolysaccharide Receptors; D011994:Recombinant Proteins; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor