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

J. C. Solheim, A. J. Reber, A. E. Ashour, S. Robinson, M. Futakuchi, S. G. Kurz, K. Hood, R. R. Fields, L. R. Shafer, D. Cornell, S. Sutjipto, S. Zurawski, D. M. LaFace, R. K. Singh, J. E. Talmadge

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)364-371
Number of pages8
JournalCancer Gene Therapy
Volume14
Issue number4
DOIs
StatePublished - Apr 2007

Keywords

  • Breast cancer
  • Cytokine
  • Dendritic cell
  • Flt3L
  • Mammary tumor

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

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