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Isolation Protocol of Mouse Monocyte-derived Dendritic Cells and Their Subsequent In Vitro Activation with Tumor Immune Complexes
11:48

Isolation Protocol of Mouse Monocyte-derived Dendritic Cells and Their Subsequent In Vitro Activation with Tumor Immune Complexes

Published on: May 31, 2018

Potential involvement of monocyte chemoattractant protein (MCP)-1/CCL2 in IL-4-mediated tumor immunity through

Hui Wang1, Yoko Nemoto-Sasaki, Toshikazu Kondo

  • 1Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan.

International Immunopharmacology
|May 22, 2003
PubMed

Insights

Interleukin-4 (IL-4) gene transfer into colon cancer cells triggers anti-tumor immunity. Monocyte chemoattractant protein-1 (MCP-1) drives dendritic cell migration, crucial for IL-4-mediated tumor rejection.

Area of Science:

  • Immunology
  • Cancer Biology
  • Molecular Biology

Background:

  • Interleukin-4 (IL-4) gene transduction into colon 26 adenocarcinoma cells abrogates tumorigenicity.
  • This effect is mediated by the generation of anti-tumor cytotoxic T lymphocytes (CTL).

Purpose of the Study:

  • To investigate the role of dendritic cell (DC) populations and chemokine expression in IL-4-mediated tumor rejection.
  • To elucidate the specific chemokines and receptors involved in DC migration to draining lymph nodes.

Main Methods:

  • Analysis of DEC-205 and CD11c double-positive cells in mouse lymph nodes post-tumor cell injection.
  • Quantification of chemokine and receptor gene expression (MCP-1/CCL2, CCL22, CCL20, CCR2) in draining lymph nodes.
  • Administration of anti-MCP-1/CCL2 antibodies to assess the impact on tumor regression and DC migration.

Main Results:

  • IL-4-transfected cells increased DEC-205+/CD11c+ cells expressing CD86 in lymph nodes.
  • Enhanced gene expression of MCP-1/CCL2, CCL22, and CCL20 was observed in draining lymph nodes.
  • CCR2, the receptor for MCP-1/CCL2, was upregulated in draining lymph nodes, with DEC-205+ cells expressing CCR2.
  • Anti-MCP-1/CCL2 antibody administration hindered tumor regression and reduced DC numbers in lymph nodes.

Conclusions:

  • Locally produced Monocyte Chemoattractant Protein-1 (MCP-1/CCL2) is critical for IL-4-mediated tumor rejection.
  • MCP-1/CCL2 likely induces dendritic cell migration into draining lymph nodes, initiating an anti-tumor immune response.

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