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

Research output: Contribution to journalArticle

37 Citations (Scopus)

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 - Jul 1 1999

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Macrophage Inflammatory Proteins
Granulocyte-Macrophage Colony-Stimulating Factor
Dendritic Cells
Vaccination
Antigen-Presenting Cells
Neoplasms
Galactosidases
CD8 Antigens
CD4 Antigens
Chemokines
Reverse Transcription
Immunity
Enzyme-Linked Immunosorbent Assay
T-Lymphocytes
Polymerase Chain Reaction

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

Cite this

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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.",
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AU - Kielian, Tammy L

AU - Nagai, Eishi

AU - Ikubo, Akashi

AU - Rasmussen, Christine A.

AU - Suzuki, Tsuneo

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AB - 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.

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