期刊
CANCER IMMUNOLOGY IMMUNOTHERAPY
卷 55, 期 9, 页码 1052-1063出版社
SPRINGER
DOI: 10.1007/s00262-005-0093-7
关键词
apoptosis; NF kappa B; TNF-alpha; IFN-gamma; NK; IL-6; natural killer; NK
The aim of this study is to identify candidate factors which may be responsible for the functional inactivation and depletion of NK cells by tumor cells. Inhibition of NF kappa B activity by an I kappa B super-repressor in HEp2 cells, a cell line commonly used as an oral tumor model, blocked tumor-induced NK cell death, and increased the function of NK cells significantly. Increased expression of CD69 early activation antigen on NK cells as well as augmented proliferation and secretion of IFN-gamma by NK cells were observed when these cells were co-incubated with I kappa B super-repressor transfected HEp2 cells (HEp2-I kappa B-(S32AS36A)). More importantly, the secretion of IL-6 was significantly inhibited when NK cells were co-cultured with HEp2-I kappa B-(S32AS36A) cells. In addition, the survival and function of cytotoxic effector cells remained significantly elevated in the presence of IFN-gamma-treated HEp2-I kappa B-(S32AS36A) cells when compared to either untreated or IFN-gamma-treated vector-alone transfected HEp2 cells. Similar findings to those obtained using purified peripheral blood NK cells were also observed when non-fractionated peripheral blood mononuclear cells were used in the co-cultures of immune effectors with HEp2 cell transfectants. Addition of recombinant human IL-6 to the co-cultures of immune effectors with the NF kappa B knockdown HEp2 tumor cells substantially decreased the levels of secreted IFN-gamma. Thus, the results presented in this paper suggest that the inhibition of NF kappa B function in oral tumors may serve to activate and expand the function and numbers of NK cells. Moreover, NF kappa B-mediated increase in IL-6 secretion by oral tumors may in part be responsible for the observed inactivation and death of the immune effectors.
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