Fractalkine transgene induces T-cell-dependent antitumor immunity through chemoattraction and activation of dendritic cells

Int J Cancer. 2003 Jan 10;103(2):212-20. doi: 10.1002/ijc.10816.


Fractalkine (FK, also called neurotactin or CX3CL1) is a CX3C chemokine that can chemoattract T lymphocytes, monocytes and NK cells. In our study, we investigated the induction of antitumor response by FK gene transfer. FK gene-modified 3LL lung carcinoma cells (3LL-FK) could both secrete soluble form and express membrane-bound form of FK. The tumor growth of 3LL-FK was decreased. Vaccination with 3LL-FK was effective in the induction of protective immunity and CTL. In vivo depletion analysis demonstrated that CD8(+) T cells are the main participating cells of the antitumor response. Obvious infiltrations of CD8(+) T cells, CD4(+) T cells and dendritic cells (DC) were observed in the tumor sites, suggesting that 3LL-FK might induce antitumor immunity through chemoattraction and activation of T cells and DC. Then we investigated the chemoattraction and activation of DC by 3LL-FK. Chemotaxis assay showed that the supernatants of 3LL-FK could chemoattract immature DC, which were found to express FK receptor CX3CR1, and the immature DC could obviously adhere to 3LL-FK. Adherence of DC to 3LL-FK resulted in phenotypic maturation and upregulated IL-12 secretion of DC, and more strong stimulation of allogeneic T-cell proliferation by DC. The increased production of IL-2 and IFNgamma in 3LL-FK tumor tissue was also observed. Our data suggested that FK gene transfer to tumor cells could induce T-cell-dependent antitumor immunity through chemoattraction and activation of DC.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • CX3C Chemokine Receptor 1
  • Carcinoma, Lewis Lung / genetics
  • Carcinoma, Lewis Lung / immunology*
  • Cell Adhesion
  • Chemokine CCL22
  • Chemokine CX3CL1
  • Chemokines, CC / metabolism
  • Chemokines, CX3C / genetics*
  • Chemokines, CX3C / metabolism
  • DNA Primers / chemistry
  • Dendritic Cells / immunology*
  • Female
  • Genetic Therapy / methods*
  • Genetic Vectors / administration & dosage
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Injections, Intralesional
  • Interferon-gamma / immunology
  • Interleukin-12 / immunology
  • Interleukin-12 / metabolism
  • Interleukin-2 / immunology
  • Interleukin-4 / metabolism
  • Lung Neoplasms / genetics
  • Lung Neoplasms / immunology*
  • Lymphocyte Activation
  • Lymphocyte Depletion
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Polymerase Chain Reaction
  • Receptors, Cytokine / metabolism
  • Receptors, HIV / metabolism
  • T-Lymphocytes, Cytotoxic / immunology*
  • Transfection
  • Transgenes


  • CX3C Chemokine Receptor 1
  • Ccl22 protein, mouse
  • Chemokine CCL22
  • Chemokine CX3CL1
  • Chemokines, CC
  • Chemokines, CX3C
  • Cx3cl1 protein, mouse
  • DNA Primers
  • Interleukin-2
  • Membrane Proteins
  • Receptors, Cytokine
  • Receptors, HIV
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor