Preoperative mobilization of circulating dendritic cells by Flt3 ligand administration to patients with metastatic colon cancer.
OBJECTIVE
To evaluate preoperative dendritic cell (DC) mobilization and tumor infiltration after administration of Flt3 ligand (Flt3L) to patients with metastatic colon cancer.


METHODS
Twelve patients with colon cancer metastatic to the liver or lung received Flt3L (20 microg/kg/d subcutaneously for 14 days for one to three cycles at monthly intervals) before attempted metastasectomy. The number and phenotype of DCs mobilized into peripheral-blood mononuclear cells (PBMCs) were evaluated by flow cytometry. After surgical resection, metastatic tumor tissue was evaluated for DC infiltration. In vivo immune responses to recall antigens were measured.


RESULTS
After Flt3L administration, on average, the total number of leukocytes in the peripheral blood increased from 5.9 +/- 1.0 x 10(3)/mm(3) to 11.2 +/- 3.8 x 10(3)/mm(3) (mean +/- SD, P: =. 0001). The percentage of CD11c(+)CD14(-) DCs in PBMCs increased from 2.4% +/- 1.8% to 8.8% +/- 4.7% (P: =.004). Delayed-type hypersensitivity (DTH) responses to recall antigens (CANDIDA:, mumps, and tetanus) showed marginally significant increases in reactivity after Flt3L administration (P: =.06, P: =.03, and P: =.08, respectively). An increase in the number of DCs was observed at the periphery of the tumors of patients who received Flt3L compared with those of patients who had not.


CONCLUSIONS
Flt3L is capable of mobilizing DCs into the peripheral blood of patients with metastatic colon cancer and may be associated with increases in DC infiltration in the peritumoral regions. Flt3L mobilization is associated with a trend toward increased DTH responses to recall antigens in vivo. The use of Flt3L to increase circulating DCs for cancer immunotherapy should be considered.
Morse
M A
MA
Departments of Medicine, Surgery, Immunology, and Pathology, Duke University Medical Center, Durham, NC 27710, USA.
Nair
S
S
Fernandez-Casal
M
M
Deng
Y
Y
St Peter
M
M
Williams
R
R
Hobeika
A
A
Mosca
P
P
Clay
T
T
Cumming
R I
RI
Fisher
E
E
Clavien
P
P
Proia
A D
AD
Niedzwiecki
D
D
Caron
D
D
Lyerly
H K
HK
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000941:Antigens / Q000276:immunology; D001772:Blood Cell Count; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000601:surgery; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D016130:Immunophenotyping; D016233:Immunotherapy, Active / Q000379:methods*; D007694:Killer Cells, Natural / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008113:Liver Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000556:secondary; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology
D000276:Adjuvants, Immunologic; D000941:Antigens; D008565:Membrane Proteins; C084881:flt3 ligand protein