Granulocyte/macrophage-colony-stimulating factor released by adenovirally transduced CT26 cells leads to the local expression of macrophage inflammatory protein 1α and accumulation of dendritic cells at vaccination sites in vivo

Tammy Kielian, Eishi Nagai, Akashi Ikubo, Christine A. Rasmussen, Tsuneo Suzuki

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Antigen presenting cells (APC) play an essential role in the generation of tumor-specific immune responses. Dendritic cells are the most potent of APC, capable of activating both antigen-specific CD4+ and CD8+ T cells. Previously, we have described how vaccination of mice with irradiated tumor cells producing granulocyte/macrophage-colony-stimulating factor (GM-CSF) induces tumor-specific immunity capable of protecting mice from a subsequent tumor challenge. The present study extends these findings to examine the types of APC infiltrating vaccination sites and the chemokines responsible for their recruitment. GM-CSF released from genetically engineered tumor cells led to the local accumulation of dendritic cells in and around the vaccination site. Quantification revealed a significant tenfold increase in the number of dendritic cells infiltrating GM-CSF-producing as opposed to β- galactosidase-producing (control) vaccination sites. Reverse transcription/polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemical analysis of vaccination sites revealed that MIP-1α may be responsible for dendritic cell infiltration into GM-CSF-producing tissues. These findings suggest that GM-CSF may indirectly recruit dendritic cells into vaccination sites through the local production of MIP-1α.

Original languageEnglish (US)
Pages (from-to)123-131
Number of pages9
JournalCancer Immunology Immunotherapy
Volume48
Issue number2-3
DOIs
StatePublished - 1999
Externally publishedYes

Keywords

  • Adenovirus
  • Dendritic cell
  • GM-CSF
  • MIP-1α
  • Vaccine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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