Preoperative mobilization of circulating dendritic cells by Flt3 ligand administration to patients with metastatic colon cancer

Purpose: to evaluate preoperative dendritic cell (DC) mobilization and tumo r infiltration after administration of Flt3 ligand (Flt3L) to patients with metastatic colon cancer. Patients and Methods: Twelve patients with colon cancer metastatic to the l iver or lung received Flt3L (20 mug/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 ce lls (PBMCs) were evaluated by flow cytometry. After surgical resection, met astatic tumor tissue was evaluated for DC infiltration. In vivo immune resp onses to recall antigens were measured. Results: After Flt3L administration, on average, the total number of leukoc ytes in the peripheral blood increased from 5.9 +/- 1.0 x 10(3)/mm(3) to 11 .2 +/- 3.8 x 103/mm3 (mean +/- SD, P = .0001). The percentage of CD11c(+)CD 14(-) 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 tumor s of patients who received Flt3L compared with those of patients who had no t. Conclusion: 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 assoc iated with a trend toward increased DTH responses to recall antigens in viv o. The use of Flt3L to increase circulating DCs for cancer immunotherapy sh ould be considered. (C) 2000 by American Society of Clinical Oncology.