ENHANCED IN-VIVO GROWTH AND RESISTANCE TO REJECTION OF TUMOR-CELLS EXPRESSING DOMINANT-NEGATIVE IFN-GAMMA RECEPTORS
ENHANCED IN-VIVO GROWTH AND RESISTANCE TO REJECTION OF TUMOR-CELLS EXPRESSING DOMINANT-NEGATIVE IFN-GAMMA RECEPTORS
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DOI：
10.1016/1074-7613(94)90087-6
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发表时间：
1994-09-01
期刊：
影响因子：
32.4
通讯作者：
SCHREIBER, RD
中科院分区：
文献类型：
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作者：
DIGHE, AS;RICHARDS, E;SCHREIBER, RD
使用中和性单克隆抗体特异性的小鼠IFN-γ，我们表明，内源性产生的IFN-γ在介导LPS诱导的排斥反应的Meth A纤维肉瘤肿瘤在同基因BALB/c小鼠中起着专性作用。为了检查IFN γ作用的细胞靶点，我们通过在Meth A中稳定过表达鼠IFN γ受体α链的截短显性阴性形式来产生IFN γ不敏感的肿瘤细胞。当植入BALB/c小鼠时，与对照Meth A细胞相比，IFN γ不敏感的Meth A细胞显示出增强的致瘤性，并且当用消除对照肿瘤的浓度的LPS处理荷瘤小鼠时，没有排斥。在Meth A免疫小鼠中，IFN γ敏感的Meth A没有建立肿瘤，而IFN γ不敏感的肿瘤以进行性方式生长。此外，IFN γ不敏感的肿瘤细胞不能引起对随后的野生型肿瘤攻击的强保护性免疫。这些结果表明，IFN γ对肿瘤细胞的免疫原性具有直接作用，从而在促进肿瘤细胞识别和消除中起重要作用。
Using a neutralizing monoclonal antibody specific for murine IFN gamma we show that endogenously produced IFN gamma plays an obligate role in mediating LPS-induced rejection of the Meth A fibrosarcoma tumor in syngeneic BALB/c mice. To examine the cellular targets of IFN gamma action, we generated IFN gamma-insensitive tumor cells by stably overexpressing in Meth A a truncated dominant negative form of the murine IFN gamma receptor alpha chain. When implanted in BALB/c mice, IFN gamma-insensitive Meth A cells displayed enhanced tumorigenicity compared with control Meth A cells and were not rejected when tumor-bearing mice were treated with concentrations of LPS that eliminated control tumors. In Meth A immune mice, IFN gamma-sensitive Meth A did not establish tumors while IFN gamma-insensitive tumors grew in a progressive manner. In addition, the IFN gamma-insensitive tumor cells were unable to elicit strong protective immunity to subsequent wild-type tumor challenge. These results show that IFN gamma has direct effects on tumor cell immunogenicity and thus plays an important role in promoting tumor cell recognition and elimination.