Peer-Reviewed Journal Details
Mandatory Fields
Ryan, AE,Shanahan, F,O'Connell, J,Houston, AM
2006
February
Cell Cycle
Fas ligand promotes tumor immune evasion of colon cancer in vivo
Published
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Optional Fields
fas ligand tumor development immune privilege anti-inflammatory antisense inhibition CD95 LIGAND CELL APOPTOSIS UP-REGULATION EXPRESSION COUNTERATTACK LYMPHOCYTES PRIVILEGE CARCINOMA INFLAMMATION ACTIVATION
5
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The study of the role of Fas ligand (FasL/CD95L) in tumor immune evasion has been complicated by the discovery that FasL may trigger cytokine secretion and induce inflammation. Antisense suppression of FasL expression by colon tumor cells was used to investigate if a reduction in endogenously expressed FasL in tumors resulted in reduced tumor development and improved anti-tumor immune challenge in vivo. Downregulation of FasL expression had no effect on tumor growth in vitro but significantly reduced tumor development in syngeneic immune-competent mice in vivo. Tumor size was also significantly decreased. Reduced FasL expression by tumor cells was associated with increased lymphocyte infiltration. Moreover, constitutively expressed FasL was not pro-inflammatory. This study indicates that upregulation of FasL expression by colon tumor cells results in an improved anti-tumor immune challenge in vivo, providing functional evidence in favor of the 'Fas counterattack' as a mechanism of tumor immune evasion.
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