Resolving the Fas counterattack controversy: Fas ligand promotes tumour immune evasion of colon cancer in vivo

Aims: To investigate if suppression of endogenous Fas Ligand (FasL) expression in colon tumour cells results in reduced tumour development in vivo.

Methods: FasL expression in CMT93 colon carcinoma cells was downregulated following stable transfection with a plasmid encoding antisense FasL cDNA. Stably transfected cells were characterized in vitro and the rate of tumour formation and growth of these FasL Low/-ve cells relative to that of both FasL +ve non-specific transfected cells and parental cells in syngeneic C57BL/6 mice was assessed in vivo.

Results: No significant difference was seen in the proliferation of the FasL Low/-ve tumour cells compared to the parental cells in vitro. However, downregulation of endogenous FasL expression significantly reduced tumour development in vivo in syngeneic immune-competent mice (p=0.024). Antisense suppression of FasL expression in colon tumour cells resulted in a 50% reduction in tumour formation. By week 6, 14 mice injected with cells transfected with a non-specific cDNA sequence developed tumours, compared to just 6 tumours in mice injected with FasL Low/-ve tumour cells.

Conclusions: Downregulation of FasL expression by colon tumours results in an improved anti-tumour immune challenge in vivo, providing definite functional evidence in favour of the 'Fas counterattack' as a mechanism of tumour immune evasion.