CD95L mediates tumor counterattack in vitro but induces neutrophil-independent tumor rejection in vivo

Int J Cancer. 2005 Jan 1;113(1):78-87. doi: 10.1002/ijc.20538.


Many tumors express CD95L (CD178, FasL, APO-1L) and may thus kill tumor-infiltrating lymphocytes, a phenomenon called tumor counterattack. However, presently it is not clear whether tumor counterattack is a relevant immune escape mechanism. To characterize the effect of CD95L expression of tumor cells on tumor-specific T cells, we established an in vitro system with TCR tg T cells and a model tumor antigen. Preactivated antitumor T cells were able to kill CD95L(-) and CD95L(+) tumor cells. CD95L(+) tumor cells killed activated T cells in vitro and inhibited the expansion of cytotoxic antitumor T cells in mixed lymphocyte tumor reactions. In vivo CD95L expression led to delayed tumor growth or complete tumor rejection. Neutrophils were not responsible for the delayed growth of the CD95L(+) tumors tested. In mice with neutrophils deficient for important cytotoxicity mechanisms (p47phox(-/-) or iNOS(-/-) mice), CD95L(+) tumors grew similarly as in wild-type mice. Incidence and growth rate of CD95L(+) tumors in mice injected with a neutrophil-depleting or an isotype control antibody was the same. In CD95-deficient lpr mice, tumor growth was not altered as compared to wild-type mice. Taken together, CD95L mediated tumor counterattack in vitro, but led to neutrophil-independent tumor rejection in vivo.

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • Cytotoxicity, Immunologic*
  • Fas Ligand Protein
  • Female
  • Gene Expression Regulation, Neoplastic
  • Membrane Glycoproteins / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Mice, Nude
  • NADPH Oxidases
  • Neoplasms, Experimental / immunology*
  • Neutrophils / metabolism
  • Nitric Oxide Synthase / deficiency
  • Nitric Oxide Synthase Type II
  • Phosphoproteins / deficiency
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes, Cytotoxic / immunology*
  • fas Receptor / immunology*


  • Fas Ligand Protein
  • Fasl protein, mouse
  • Membrane Glycoproteins
  • Phosphoproteins
  • fas Receptor
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • NADPH Oxidases
  • neutrophil cytosolic factor 1