Antitumor immune response by CX3CL1 fractalkine gene transfer depends on both NK and T cells

Eur J Immunol. 2005 May;35(5):1371-80. doi: 10.1002/eji.200526042.


The CX3C chemokine fractalkine (CX3CL1) exists as both a membrane-bound form promoting firm cell-cell adhesion and a soluble form chemoattracting leukocytes expressing its receptor CX3CR1. When adenoviral vector expressing mouse fractalkine (AdFKN) was transduced to the tumor cells, fractalkine was expressed as both membrane-bound form on the tumor cells and soluble form in the supernatant in vitro. Intratumoral injection of AdFKN (1 x 10(9)PFU/tumor) into C26 and B16F10 tumors resulted in marked reduction of tumor growth compared to control (C26: 86.5%, p<0.001; B16F10: 85.5%, p<0.001). Histological examination of tumor tissues revealed abundant infiltration of NK cells, dendritic cells, and CD8(+) T lymphocytes 3 and/or 6 days after treatment with AdFKN. Splenocytes from mice treated by AdFKN developed tumor-specific cytotoxic T cells, and thereby protected from rechallenging with parental tumor cells. Antitumor effects by AdFKN were completely abrogated in both NK cell-depleted mice and CD8(-/-) mice, and partially blocked in CD4(-/-) mice. These data indicated that fractalkine mediates antitumor effects by both NK cell-dependent and T cell-dependent mechanisms. This study suggests that fractalkine can be a suitable candidate for immunogene therapy of cancer because fractalkine induces both innate and adaptive immunity.

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Line, Tumor
  • Chemokine CX3CL1
  • Chemokines, CX3C / genetics
  • Chemokines, CX3C / immunology*
  • Flow Cytometry
  • Genetic Therapy*
  • Killer Cells, Natural / immunology*
  • Lymphocyte Subsets / immunology*
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology*
  • Mice
  • Neoplasms / immunology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / immunology*
  • Transduction, Genetic


  • Chemokine CX3CL1
  • Chemokines, CX3C
  • Cx3cl1 protein, mouse
  • Membrane Proteins