Fas ligand on tumor cells mediates inactivation of neutrophils

研究成果: Article

52 引文 斯高帕斯(Scopus)

摘要

The expression of Fas ligand (FasL) on tumor cells (tumor FasL) has been implicated in their evasion of immune surveillance. In this study, we investigated the cellular mechanism for FasL-associated immune escape using melanoma B16F10-derived cells as a model. Transfectants carrying FasL-specific ribozymes expressed low levels of FasL (FasLlow tumor cells) as compared with those carrying enhanced green fluorescent protein-N1 plasmids (FasLhigh tumor cells). When injected s.c. into C57BL/6 mice, FasLlow tumor cells grew more slowly than did FasLhigh melanoma cells. FasLhigh tumor cells showed more intensive neutrophilic infiltration accompanied by multiple necrotizing areas than did FasLlow tumor cells. The average size of FasLlow tumors, but not of FasLhigh tumors, was significantly enhanced in mice depleted of neutrophils. Consistently, a local injection of LPS to recruit/activate neutrophils significantly delayed tumor formation by FasLlow tumor cells, and slightly retarded that of FasLhigh tumor cells in both C57BL/6 and nonobese diabetic/SCID mice. Neutrophils killed FasLlow melanoma cells more effectively than FasLhigh melanoma cells in vitro. The resistance of FasLhigh melanoma cells to being killed by neutrophils was correlated with impaired neutrophil activation, as demonstrated by reductions in gelatinase B secretion, reactive oxygen species production, and the surface expression of CD11b and the transcription of FasL. Local transfer of casein-enriched or PMA-treated neutrophils delayed tumor formation by melanoma cells. Taken together, inactivation of neutrophils by tumor FasL is an important mechanism by which tumor cells escape immune attack.

原文English
頁(從 - 到)1183-1191
頁數9
期刊Journal of Immunology
171
發行號3
DOIs
出版狀態Published - 2003 八月 1

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

指紋 深入研究「Fas ligand on tumor cells mediates inactivation of neutrophils」主題。共同形成了獨特的指紋。

  • 引用此