The influence of CD95L expression on tumor rejection in mice
The influence of CD95L expression on tumor rejection in mice
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DOI：
10.1002/eji.200324176
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发表时间：
2003-10-01
影响因子：
5.4
通讯作者：
Krammer, PH
中科院分区：
文献类型：
--
作者：
Igney, FH;Behrens, CK;Krammer, PH
许多肿瘤表达死亡配体CD95L (CD178、APO-1L、FasL)，并能在体外杀死活化的T细胞。这可能使肿瘤细胞抑制抗肿瘤免疫反应，这种现象被称为“肿瘤反击”。在人类肿瘤中存在肿瘤反击的初步证据。然而，表达cd95l的肿瘤在小鼠体内迅速被排斥。为了澄清这一有争议的情况，我们研究了CD95L表达的水平或时间点是否可能是决定肿瘤反击或肿瘤排斥的关键因素。我们产生了表达不同水平CD95L （LKC-CD95L）的cd95耐药肿瘤细胞系。在裸鼠中，CD95L表达水平对CD95L肿瘤的生长无影响。相比之下，CD95L（-）对照肿瘤细胞系（LKC）生长得更快。此外，我们通过tet系统诱导CD95L生成了cd95抗性细胞系（LKCR-tetCD95L）。在裸鼠和NOD/SCID小鼠的肿瘤中诱导CD95L导致肿瘤的快速排斥反应。诱导低CD95L表达水平仅轻微延迟肿瘤排斥反应。这些结果表明，小鼠对表达CD95L的肿瘤的排斥不是过度表达的结果，也不依赖于肿瘤进展开始时CD95L的存在。
Many tumors express the death ligand CD95L (CD178, APO-1L, FasL) and can kill activated T cells in vitro. This may enable the tumor cells to suppress anti-tumor immune responses, a phenomenon called "tumor counterattack". Preliminary evidence of tumor counterattack in human tumors exists. However, CD95L-expressing tumors are rapidly rejected in mice. In order to clarify this controversial situation we investigated whether the level or the time point of CD95L expression might be critical factors determining tumor counterattack versus tumor rejection. We generated CD95-resistant tumor cell lines expressing different levels of CD95L (LKC-CD95L). In nude mice the CD95L expression level had no influence on the growth of the CD95L tumors. In contrast, a CD95L(-) control tumor cell line (LKC) grew much faster. In addition, we generated a CD95-resistant cell line in which CD95L was induced via the tet system (LKCR-tetCD95L). Induction of CD95L in established tumors in nude and NOD/SCID mice led to rapid rejection of the tumors. Induction of lower CD95L expression levels delayed tumor rejection only marginally. These results demonstrate that rejection of CD95L-expressing tumors in mice is not a result of overexpression and does not depend on the presence of CD95L at the onset of tumor progression.