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Spleen but not tumor infiltration by dendritic and T cells is increased by intravenous adenovirus-Flt3 ligand injection

Cancer Gene Therapy volume 14, pages 364–371 (2007)Cite this article

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.

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Acknowledgements

We gratefully acknowledge the assistance of the University of Nebraska Medical Center Cell Analysis Facility and Animal Facility. This work was supported by the Nebraska Research Initiative Programs in Molecular Therapeutics and Clinical Translation of Biotechnology (JET, RKS, and JCS), and by an Eppley Cancer Center Grant (JCS). AJR was supported by a DOD Breast Cancer Training Program postdoctoral fellowship (DAMD 17-00-1-0361), and AEA received support from a UNMC Graduate Studies Research Assistantship.

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Authors and Affiliations

  1. Eppley Institute, University of Nebraska Medical Center, Omaha, Nebraska, USA

    J C Solheim & A J Reber

  2. Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, USA

    A E Ashour, M Futakuchi, S G Kurz, K Hood, R R Fields, L R Shafer, R K Singh & J E Talmadge

  3. MD Anderson Cancer Center, The University of Texas, Houston, TX, USA

    S Robinson

  4. Canji Inc., San Diego, CA, USA

    D Cornell, S Sutjipto & D M LaFace

  5. DNAX Research Institute, Palo Alto, CA, USA

    S Zurawski

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  1. J C Solheim
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Correspondence to J C Solheim.

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Solheim, J., Reber, A., Ashour, A. et al. Spleen but not tumor infiltration by dendritic and T cells is increased by intravenous adenovirus-Flt3 ligand injection. Cancer Gene Ther 14, 364–371 (2007). https://doi.org/10.1038/sj.cgt.7701018

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  • DOI: https://doi.org/10.1038/sj.cgt.7701018

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