Dendritic cells engineered to express GITRL enhance therapeutic immunity in murine Lewis lung carcinoma

Cancer Lett. 2011 Feb 28;301(2):142-50. doi: 10.1016/j.canlet.2010.11.005. Epub 2010 Dec 24.

Abstract

Glucocorticoid-induced tumor necrosis factor receptor and its ligand (GITRL) are critically involved in the regulation of immune response. In this study, we aimed to generate bone marrow-derived dendritic cells (BMDCs) transfected with recombinant adenovirus expressing GITRL (pAd-GITRL-BMDCs) and explore their therapeutic efficacy in murine Lewis lung carcinoma. In vitro, pAd-GITRL-BMDCs greatly enhanced effector T cells proliferation but markedly abrogate the suppression of Treg cells. Moreover, vaccination with pAd-GITRL-BMDCs significantly retarded tumor growth, which was accompanied with increased IFN-γ-producing CD8+ T cells and markedly decreased Treg cells in vivo. These findings suggest GITRL could enhance the immune stimulation of DC and might facilitate the potential development of DCs-based anti-tumor therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Carcinoma, Lewis Lung / immunology*
  • Carcinoma, Lewis Lung / pathology
  • Carcinoma, Lewis Lung / therapy
  • Cell Line, Tumor
  • Cell Proliferation
  • Cells, Cultured
  • Coculture Techniques
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dendritic Cells / transplantation
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Genetic Vectors / genetics
  • HEK293 Cells
  • Humans
  • Immunophenotyping
  • Immunotherapy, Adoptive
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Transduction, Genetic*
  • Tumor Burden / immunology
  • Tumor Necrosis Factors / genetics
  • Tumor Necrosis Factors / immunology*
  • Tumor Necrosis Factors / metabolism

Substances

  • Tnfsf18 protein, mouse
  • Tumor Necrosis Factors
  • Interferon-gamma