Spleen but not tumor infiltration by dendritic and T cells is increased by intravenous adenovirus-Flt3 ligand injection.
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.
Solheim
J C
JC
Eppley Institute, University of Nebraska Medical Center, Omaha, Nebraska 68198-6805, USA. jsolheim@unmc.edu
Reber
A J
AJ
Ashour
A E
AE
Robinson
S
S
Futakuchi
M
M
Kurz
S G
SG
Hood
K
K
Fields
R R
RR
Shafer
L R
LR
Cornell
D
D
Sutjipto
S
S
Zurawski
S
S
LaFace
D M
DM
Singh
R K
RK
Talmadge
J E
JE
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
D008565:Membrane Proteins; C084881:flt3 ligand protein