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Critical Reviews™ in Immunology
IF: 1.352 5-Year IF: 3.347 SJR: 0.657 SNIP: 0.55 CiteScore™: 2.19

ISSN Print: 1040-8401
ISSN Online: 2162-6472

Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v18.i1-2.110
pages 99-107

Induction of Dendritic Cells (DC) by Flt3 Ligand (FL) Promotes the Generation of Tumor-Specific Immune Responses In Vivo

David H. Lynch
Department of Immunobiology, Immunex Corporation, 51 University Street, Seattle, WA 98101

ABSTRACT

Daily treatment of mice with human Flt3 ligand (FL) induces the production of large numbers of ÌÍÑ-class II+, CDllc+, DEC205+ dendritic cells (DC) in both lymphoid and nonlymphoid tissues. Because DC play a pivotal role in the induction of immune responses, we evaluated the effects of FL in the augmentation of anti-tumor immune responses in vivo. Treatment with daily subcutaneous injections of FL not only caused complete regression of tumors in a significant proportion of mice challenged with a syngeneic methylcholanthrene-induced fibrosarcoma, but also caused a significant decrease in the tumor growth rate in the remaining mice. The effects of FL were both dose and schedule dependent, induced regression of tumors established as much as 7 days prior to beginning cytokine treatment, and was mediated by both T-cell-mediated and non-T-cell-mediated mechanisms. Histopathologic evaluation of tumors during and after systemic treatment with FL revealed a dense infiltration of mononuclear and myeloid precursor cells into both the tumor and tissue surrounding the tumor that generally correlated with the degree of regression and resolved after rejection of the tumor. Collectively, the data suggest that FL may be an important cytokine in the generation of effective anti-tumor immune responses in vivo and the treatment of cancer in situ.


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