期刊
JOURNAL OF IMMUNOLOGY
卷 171, 期 3, 页码 1183-1191出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.171.3.1183
关键词
-
类别
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 (FasL(low) tumor cells) as compared with those carrying enhanced green fluorescent protein-N1 plasmids (FasL(high) tumor cells). When injected s.c. into C57BL/6 mice, FasL(low) tumor cells grew more slowly than did FasL(high) melanoma cells. FasL(high) tumor cells showed more intensive neutrophilic infiltration accompanied by multiple necrotizing areas than did FasL(low) tumor cells. The average size of FasL(low) tumors, but not of FasL(high) tumors, was significantly enhanced in mice depleted of neutrophils. Consistently, a local injection of LPS to recruit/activate neutrophils significantly delayed tumor formation by FasL(low) tumor cells, and slightly retarded that of FasL high tumor cells in both C57BL/6 and nonobese diabetic/SCID mice. Neutrophils killed FasL(low) melanoma cells more effectively than FasL high melanoma cells in vitro. The resistance of FasL high 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据