title: Spleen but not tumor infiltration by dendritic and T cells is increased by intravenous adenovirus-Flt3 ligand injection.
abstract: Dendritic cell (DC) expansion is regulated by the hematopoietic growth factor fms-like tyrosine kinase 3 ligand (Flt3L). DCs are critical to the control of tumor growth and metastasis, and there is a positive correlation between intratumoral DC infiltration and clinical outcome. In this report, we first demonstrate that single intravenous (i.v.) injections of adenovirus (Adv)-Flt3L significantly increased splenic dendritic, B, T and natural killer (NK) cell numbers in both normal and mammary tumor-bearing mice. In contrast, the numbers of DCs and T cells infiltrating the tumors were not increased. Consistent with the minimal effect on immune cell infiltration, i.v. Adv-Flt3L injections had no therapeutic activity against orthotopic mammary tumors. In addition, we noted tumor and Adv-Flt3L expansion of Gr1(+)CD11b(+) immature myeloid suppressor cells (IMSCs), which may inhibit the therapeutic efficacy of Adv-Flt3L-expanded DCs.
authors.affiliation: Eppley Institute, University of Nebraska Medical Center, Omaha, Nebraska 68198-6805, USA. jsolheim@unmc.edu
authors.forename: J C
authors.initials: JC
authors.lastname: Solheim
authors.forename: A J
authors.initials: AJ
authors.lastname: Reber
authors.forename: A E
authors.initials: AE
authors.lastname: Ashour
authors.forename: S
authors.initials: S
authors.lastname: Robinson
authors.forename: M
authors.initials: M
authors.lastname: Futakuchi
authors.forename: S G
authors.initials: SG
authors.lastname: Kurz
authors.forename: K
authors.initials: K
authors.lastname: Hood
authors.forename: R R
authors.initials: RR
authors.lastname: Fields
authors.forename: L R
authors.initials: LR
authors.lastname: Shafer
authors.forename: D
authors.initials: D
authors.lastname: Cornell
authors.forename: S
authors.initials: S
authors.lastname: Sutjipto
authors.forename: S
authors.initials: S
authors.lastname: Zurawski
authors.forename: D M
authors.initials: DM
authors.lastname: LaFace
authors.forename: R K
authors.initials: RK
authors.lastname: Singh
authors.forename: J E
authors.initials: JE
authors.lastname: Talmadge
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D007275:Injections, Intravenous; D018655:Lymphocyte Count; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D015674:Mammary Neoplasms, Animal / Q000628:therapy*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D017211:Treatment Failure
chemical_list: D008565:Membrane Proteins; C084881:flt3 ligand protein