FLT3-LIGAND ADMINISTRATION INHIBITS LIVER METASTASES - ROLE OF NK CELLS

FLT3-1igand (FL) is a recently described cytokine that stimulates the proliferation and differentiation of hematopoietic progenitors both in vivo and in vitro and, when administered to mice, induces an accumula tion of dendritic cells (DC) in different lymphoid and nonlymphoid org ans and tissues, including the liver, We have studied the antitumor ef fect of FL administered alone or in combination with IL-12 in a day 3 murine liver metastasis model, FL significantly reduced the number of hepatic metastases (36.00 +/- 11.00 vs 92.00 +/- 10.19 in control grou p, p < 0.05), Histologic evaluation of the livers revealed that FL ind uced a significant infiltration of the tumor border by lymphocytes and DC associated with increased number of apoptotic figures, Immunohisto chemical analysis demonstrated that FL significantly enhanced the numb er of DC in the liver parenchyma and within the liver metastases, as w ell as the number of CD4(+) and CD8(+) T lymphocytes. These data suppo rt the suggestion that DC may be directly involved in the antitumor ef fect of FL, Interestingly, the antitumor effect of FL was greatly redu ced by the NH depletion. Combination of FL and IL-12 resulted in great er antitumor efficacy than these cytokines alone, In summary, we have shown that FL has significant antitumor effect on preexisting murine C 3 liver tumors that is mediated by MC cells, We have also demonstrated that the FL/IL-12 combination has an enhanced antitumor activity in t he same murine turner model.