Igney Frederik H, Behrens Christian K, Krammer Peter H
Tumor Immunology Program, German Cancer Research Center, Heidelberg, Germany.
Eur J Immunol. 2003 Oct;33(10):2811-21. doi: 10.1002/eji.200324176.
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 CD95Lin 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.
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。这可能使肿瘤细胞能够抑制抗肿瘤免疫反应，这种现象称为“肿瘤反击”。人类肿瘤中存在肿瘤反击的初步证据。然而，表达CD95L的肿瘤在小鼠中会迅速被排斥。为了澄清这种有争议的情况，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与肿瘤排斥的关键因素。我们构建了表达不同水平CD95L的抗CD95肿瘤细胞系（LKC-CD95L）。在裸鼠中，CD95L表达水平对CD95L(+)肿瘤的生长没有影响。相比之下，CD95L(-)对照肿瘤细胞系（LKC）生长得快得多。此外，我们构建了一个抗CD95细胞系，其中CD95L通过四环素系统诱导表达（LKCR-tetCD95L）。在裸鼠和NOD/SCID小鼠的已建立肿瘤中诱导CD95L表达会导致肿瘤迅速被排斥。诱导较低水平的CD95L表达只会轻微延迟肿瘤排斥。这些结果表明，小鼠中表达CD95L的肿瘤被排斥不是过表达的结果，也不依赖于肿瘤进展开始时CD95L的存在。
