Chemoattraction, adhesion and activation of natural killer cells are involved in the antitumor immune response induced by fractalkine/CX3CL1

Immunol Lett. 2003 Oct 9;89(1):1-7. doi: 10.1016/s0165-2478(03)00101-9.


Fractalkine (FK, also called neurotactin or CX3CL1) is a CX3C chemokine that can chemoattract T lymphocytes, monocytes, dendritic cells (DC) and natural killer (NK) cells. One of our previous studies demonstrated that FK in soluble form can chemoattract T cells and DC and membrane-bound FK can adhere T cells and DC. Vaccination with 3LL lung carcinoma cells gene-modified with FK (3LL-FK) induces potent antitumor CTL response. The aim of the present study is to investigate whether NK cells participate in FK-induced antitumor immunity. We found that NK activity was increased in mice inoculated with 3LL-FK and in vivo depletion of NK cells resulted in the decreased tumor growth inhibition of 3LL-FK, indicating that NK cells play an important role in the antitumor immunity induced by FK. Further studies showed 3LL-FK could chemoattract, adhere NK cells and attract more NK cells to infiltrate into tumor tissue. Incubation of NK cells with 3LL-FK could increase the cytotoxicity of NK cells against YAC-1 cells and even against NK-resistant parental 3LL cells. IL-12 production increased more significantly in the 3LL-FK tumor nodules. Taken together with CTL response induced by 3LL-FK, our data demonstrate that FK, expressed by gene-modified tumor cells, can induce potent antitumor effect through different mechanisms, one of which involves chemoattraction of NK cells into tumor sites and activation of NK cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cancer Vaccines / immunology*
  • Cancer Vaccines / therapeutic use
  • Carcinoma, Lewis Lung / immunology*
  • Cell Adhesion
  • Chemokine CX3CL1
  • Chemokines, CX3C / genetics
  • Chemokines, CX3C / immunology*
  • Chemotaxis, Leukocyte*
  • Coculture Techniques
  • Cytotoxicity, Immunologic
  • Female
  • Flow Cytometry
  • Genetic Therapy
  • Interleukin-12 / biosynthesis
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / physiology
  • Lymphocyte Activation*
  • Lymphocyte Depletion
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology*
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocytes / immunology
  • Transfection
  • Vaccination


  • Cancer Vaccines
  • Chemokine CX3CL1
  • Chemokines, CX3C
  • Cx3cl1 protein, mouse
  • Membrane Proteins
  • Interleukin-12