Interleukin-17 inhibits tumor cell growth by means of a T-cell-dependent mechanism
Interleukin-17 inhibits tumor cell growth by means of a T-cell-dependent mechanism
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DOI：
10.1182/blood.v99.6.2114
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发表时间：
2002-03-15
期刊：
影响因子：
20.3
通讯作者：
Tartour, E
中科院分区：
文献类型：
--
作者：
Benchetrit, F;Ciree, A;Tartour, E
白细胞介素17（IL-17）是由活化的CD 4（+）记忆T细胞产生的促炎细胞因子。我们先前表明IL-17增加了移植到无胸腺裸鼠中的人宫颈肿瘤的生长速率。为了解决T细胞在IL-17的生物活性中对肿瘤控制的可能作用，我们将用编码鼠IL-17的互补DNA转染的2个鼠造血免疫原性肿瘤（P815和J558 L）移植到同基因免疫活性小鼠中。我们发现，与模拟转染的肿瘤相比，2个IL-17产生肿瘤的生长被显著抑制。与在免疫活性小鼠中观察到的IL-17的抗肿瘤活性相反，我们观察到移植到裸鼠中的IL-17转染或模拟转染的P815细胞（分别为P815-IL-17和P815-Neo）的体内生长没有差异。然后，我们发现IL-17增加了针对来自P815的免疫显性抗原（称为A、B、C、D和E）的特异性溶细胞性T淋巴细胞（CTL）的产生，因为所有用P815-IL-17注射的小鼠都产生了P815特异性CTL应答，而用P815-Neo免疫的16只小鼠中只有6只具有针对抗原的特异性CTL应答。CTL的诱导与肿瘤保护性免疫的建立相关。这些实验表明，T淋巴细胞参与IL-17的抗肿瘤活性。因此，IL-17与其他细胞因子一样，似乎是一种多效性细胞因子，对肿瘤发展具有可能的促肿瘤或抗肿瘤作用，这通常取决于肿瘤模型的免疫原性。
Interleukin 17 (IL-17) is a proinflammatory cytokine produced by activated CD4(+) memory T cells. We previously showed that IL-17 increased the growth rate of human cervical tumors transplanted into athymic nude mice. To address the possible role of T cells in the biologic activity of IL-17 for tumor control, we grafted 2 murine hematopoietic immunogenic tumors (P815 and J558L) transfected with a complementary DNA encoding murine IL-17 into syngeneic immunocompetent mice. We found that growth of the 2 IL-17-producing tumors was significantly inhibited compared with that of mock-transfected tumors. In contrast to the antitumor activity of IL-17 observed in immunocompetent mice, we observed no difference in the in vivo growth of IL-17-transfected or mock-transfected P815 cells (P815-IL-17 and P815-Neo, respectively) transplanted into nude mice. We then showed that IL-17 increased generation of specific cytolytic T lymphocytes (CTLs) directed against the immunodominant antigens from P815 called A, B, C, D, and E, since all mice injected with P815-IL-17 developed a P815-specific CTL response, whereas only 6 of 16 mice immunized with P815-Neo had a specific CTL response against the antigens. The induction of CTLs was associated with establishment of a tumor-protective immunity. These experiments suggest that T lymphocytes are involved in the antitumor activity of IL-17. Therefore, IL-17, like other cytokines, appears to be a pleiotropic cytokine with possible protumor or antitumor effects on tumor development, which often depends on the immunogenicity of tumor models.