Cross-talk between tumor cells and neutrophils through the Fas (APO-1, CD95)/FasL system: human glioma cells enhance cell viability and stimulate cytokine production in neutrophils

J Leukoc Biol. 2003 Mar;73(3):363-8. doi: 10.1189/jlb.0702375.


Many tumor cells are resistant to Fas-mediated killing, which has been primarily used as a mechanism to evade immune attack. In this study, we found a new action of Fas on tumors where activation of the Fas signal may force tumor cells to produce survival factors for neutrophils. Human peripheral circulating neutrophils in coculture with glioma cells showed significant delays in spontaneous apoptosis. Interleukin (IL)-6 and IL-8 partially mediated the glioma cell-associated, protective effect on neutrophils. The Fas agonistic antibody CH-11 dose-dependently stimulated the expression of IL-6 and IL-8 in glioma cells. Accordingly, blocking the Fas/FasL interaction reduced IL-6 and IL-8 production in glioma cells and impaired their protective effect on neutrophils. Coculture with glioma cells also affected the expression of cytokines in neutrophils, including IL-8, interferon-gamma, and tumor necrosis factor alpha to various extents. Collectively, our results demonstrate bi-directional cross-talk between tumor and immune cells. Although Fas activation alone cannot induce apoptosis in tumor cells, it may potentially initiate an effective anti-tumor response through a circumvented mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Survival
  • Coculture Techniques
  • Cytokines / biosynthesis
  • Cytokines / metabolism
  • Fas Ligand Protein
  • Gene Expression Regulation
  • Glioma / metabolism*
  • Glioma / pathology
  • Humans
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / metabolism
  • Interleukin-8 / biosynthesis
  • Interleukin-8 / metabolism
  • Membrane Glycoproteins / physiology*
  • Neutrophils / cytology
  • Neutrophils / metabolism*
  • Receptor Cross-Talk / physiology*
  • Tumor Cells, Cultured
  • fas Receptor / physiology*


  • Cytokines
  • FASLG protein, human
  • Fas Ligand Protein
  • Interleukin-6
  • Interleukin-8
  • Membrane Glycoproteins
  • fas Receptor