Overexpression of interleukin‐15 in vivo enhances antitumor activity against mhc class I‐negative and ‐positive malignant melanoma through augmented NK activity and cytotoxic T‐cell response
Overexpression of interleukin‐15 in vivo enhances antitumor activity against mhc class I‐negative and ‐positive malignant melanoma through augmented NK activity and cytotoxic T‐cell response
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DOI：
10.1002/ijc.10395
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发表时间：
2002-06
影响因子：
6.4
通讯作者：
T. Yajima;H. Nishimura;W. Wajjwalku;M. Harada;H. Kuwano;Y. Yoshikai
中科院分区：
文献类型：
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作者：
T. Yajima;H. Nishimura;W. Wajjwalku;M. Harada;H. Kuwano;Y. Yoshikai
白细胞介素（IL）-15是一种多效性细胞因子，参与NK细胞和记忆性CD 8 + T细胞的发育和维持。我们使用我们最近构建的IL-15转基因（Tg）小鼠，研究了IL-15体内过表达对2种小鼠B16黑色素瘤细胞系（MHC I类阴性B16.44和MHC I类阳性B16 F10细胞）的保护作用。皮下（s.c.）接种B16.44或B16 F10细胞。IL-15 Tg小鼠显示出增强的NK细胞对B16.44细胞的活性，并且通过抗脱唾液酸GM 1 Ab处理的体内NK细胞耗竭消除了IL-15 Tg小鼠中的抗肿瘤活性。另一方面，用B16 F10细胞接种的IL-15 Tg小鼠产生了显著水平的针对B16 F10细胞的CTL应答，并且通过抗CD 8 MAb处理体内消耗CD 8 + T细胞消除了抗肿瘤活性。因此，IL-15的过表达通过增强不同的抗肿瘤机制来增强针对不同肿瘤的抗肿瘤活性。这些结果表明IL-15可能用于表达广泛MHC类分子的人肿瘤的治疗应用。© 2002 Wiley利斯公司
Interleukin (IL)‐15, a pleiotropic cytokine, is involved in the development and maintenance of NK cells and memory CD8+ T cells. We examined the effects of in vivo overexpression of IL‐15 on protection against 2 types of murine B16 melanoma lines, MHC class I‐negative B16.44 and MHC class I‐positive B16F10 cells, using IL‐15 transgenic (Tg) mice that we have recently constructed. The tumor growth was severely retarded in IL‐15 Tg mice after subcutaneous (s.c.) inoculation with B16.44 or B16F10 cells. IL‐15 Tg mice showed an augmented NK cell activity against B16.44 cells, and in vivo depletion of NK cells by anti‐asialoGM1 Ab treatment abrogated the antitumor activity in IL‐15 Tg mice. On the other hand, IL‐15 Tg mice inoculated with B16F10 cells developed a significant level of CTL response against B16F10 cells, and in vivo depletion of CD8+ T cells by anti‐CD8 MAb treatment abrogated the antitumor activity. Thus, overexpression of IL‐15 augmented antitumor activity against different tumors via augmentation of different antitumor mechanisms. These results suggest a possible therapeutic application of IL‐15 for human neoplasms expressing a wide range of MHC class molecules. © 2002 Wiley‐Liss, Inc.