SLC gene-modified dendritic cells mediate T cell-dependent anti-gastric cancer immune responses in vitro

Oncol Rep. 2013 Feb;29(2):595-604. doi: 10.3892/or.2012.2154. Epub 2012 Nov 28.

Abstract

Dendritic cells (DCs) are potent professional antigen-presenting cells (APCs) with the ability to prime naïve T cells, and play an important role in the initiation and regulation of immune responses. In this study, we constructed a recombinant adenovirus carrying the SLC gene (Ad-SLC), and detected the biological effects of Ad-SLC-modified DCs as an adjuvant for the initiation of gastric cancer immune responses. Human DCs were transfected with Ad-SLC and the recombinant adenovirus carrying the β-galactosidase gene, Ad-LacZ, respectively. Modified DCs were pulsed with the cell lysate antigen of SGC-7901 cells (a type of gastric cancer cell line) and co-cultured with autologous T cells. The T cells were harvested and incubated with SGC-7901 cells and the cytotoxic function of the T cells was detected. Based on the data, the expression of mature DC phenotypes CD83 and CCR7 was upregulated after transfection with Ad-SLC and the chemotaxis function of DCs was augmented after transfection with Ad-SLC. Moreover, the expression of RANTES in DCs was upregulated by Ad-SLC transfection, while expression levels of IL-12p70 and IL-10 were not significantly altered. When co-cultured with autologous T cells, DCs modified with the SLC gene and pulsed with SGC-7901 cell lysates significantly promoted the proliferation of autologous T cells and induced Th1 differentiation, and displayed a strong cytotoxicity to SGC-7901 cells. In conclusion, Ad-SLC promoted DC maturation, enhancing the ability of DCs for T-cell chemotaxis and T-cell stimulation, and induced specific anti-gastric cancer cellular immunity. Recombinant Ad-SLC-modified DCs may be used as an adjuvant to induce an effective anti-gastric cancer immune response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae
  • Antigens, CD / metabolism
  • CD83 Antigen
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Proliferation
  • Chemokine CCL21 / genetics*
  • Chemokine CCL5 / metabolism
  • Chemotaxis / genetics
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism*
  • Genetic Vectors
  • Humans
  • Immunity, Cellular / genetics
  • Immunoglobulins / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-12 / metabolism
  • Membrane Glycoproteins / metabolism
  • Neoplasm Proteins / genetics*
  • Phenotype
  • Receptors, CCR7 / metabolism
  • Stomach Neoplasms / immunology*
  • T-Lymphocytes / immunology*
  • Th1 Cells / physiology
  • Transfection
  • Up-Regulation / genetics

Substances

  • Antigens, CD
  • CCR7 protein, human
  • Chemokine CCL21
  • Chemokine CCL5
  • Immunoglobulins
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • Receptors, CCR7
  • Interleukin-10
  • Interleukin-12