Interleukin-28B Acts Synergistically With Cisplatin to Suppress the Growth of Head and Neck Squamous Cell Carcinoma
Interleukin-28B Acts Synergistically With Cisplatin to Suppress the Growth of Head and Neck Squamous Cell Carcinoma
复制标题
DOI：
10.1097/cji.0b013e318204ed70
复制
发表时间：
2011-03
影响因子：
3.9
通讯作者：
Koichiro Yoshimoto;T. Kishida;H. Nakano;M. Matsui;M. Shin-Ya;Taketoshi Shimada;S. Nakai;J. Imanishi;M. Takeuchi;Y. Hisa;O. Mazda
中科院分区：
文献类型：
--
作者：
Koichiro Yoshimoto;T. Kishida;H. Nakano;M. Matsui;M. Shin-Ya;Taketoshi Shimada;S. Nakai;J. Imanishi;M. Takeuchi;Y. Hisa;O. Mazda
白介素28B(IL-28B)又称干扰素-3，属于III型干扰素家族。早期的研究表明，IL-28B在体外对一些肿瘤细胞的增殖有抑制作用。IL-28B基因的体外转染也可通过直接的抗增殖作用或诱导抗肿瘤免疫而导致小鼠肿瘤细胞的生长迟缓。然而，重组IL-28B的体内治疗性给药是否能抑制预先建立的肿瘤的生长尚未见报道。在这里，我们发现，重复皮下注射重组小鼠IL-28B显著诱导肿瘤特异性细胞毒性T淋巴细胞，并增强自然杀伤细胞杀伤活性，导致适度抑制小鼠头颈部鳞状细胞癌(HNSCC)细胞系的生长，该细胞系完全抵抗IL-28B的直接抗增殖作用。此外，重组小鼠IL-28B和顺铂(CDDP)联合应用更显著地抑制了已在同基因小鼠体内建立的肿瘤的生长，并诱导了肿瘤特异性细胞毒T淋巴细胞。CDDP在体内外均可诱导HNSCC细胞表面主要组织相容性复合体I类分子和Fas分子的表达，这可能是其协同抑瘤作用的机制。与I型干扰素不同，IL-28B在培养中不抑制骨髓细胞的生长。因此，IL-28B可能作为一种新的多学科抗癌治疗的工具，显著增强先天和获得性抗肿瘤免疫反应，特别是与CDDP联合应用时，CDDP目前是包括HNSCCs在内的各种肿瘤的首选化疗药物。
Interleukin-28B (IL-28B), also referred to as interferon-3, belongs to the type III interferon family. Earlier studies showed that IL-28B suppresses proliferation of some tumor cells in vitro. IL-28B gene transfection ex vivo also resulted in growth retardation of tumor cells in mice, through either direct antiproliferative action or induction of antitumor immunity. However, it has not been reported whether in vivo therapeutic administration of recombinant IL-28B can inhibit the growth of a pre-established tumor. Here, we found that repetitive subcutaneous administration of recombinant mouse IL-28B significantly induced tumor-specific cytotoxic T lymphocytes and augmented natural killer cytolytic activity, leading to moderate suppression of the growth of a murine head and neck squamous cell carcinoma (HNSCC) cell line that was completely resistant to the direct antiproliferative effect of IL-28B. Moreover, co-administration of recombinant mouse IL-28B and cisplatin (CDDP) more significantly inhibited in vivo growth of the tumor that had been established in syngenic mice and induced tumor-specific cytotoxic T lymphocytes. The CDDP treatment induced the expression of major histocompatibility complex class I and Fas molecules on the surface of HNSCC cells both in vitro and in vivo; this may be the mechanism underlying the synergistic tumor suppression activity of IL-28B and CDDP. Unlike type I interferon, IL-28B did not suppress growth of bone marrow cells in culture. Therefore, IL-28B may be useful as a tool for a novel multidisciplinary therapy against cancer, significantly potentiating innate and adaptive antitumor immune responses, especially when co-administrated with CDDP, which is currently the first choice chemotherapeutic agent against various tumors including HNSCCs.