The CIK cells stimulated with combination of IL-2 and IL-15 provide an improved cytotoxic capacity against human lung adenocarcinoma
The CIK cells stimulated with combination of IL-2 and IL-15 provide an improved cytotoxic capacity against human lung adenocarcinoma
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DOI：
10.1007/s13277-013-1265-2
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发表时间：
2014-03
期刊：
影响因子：
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通讯作者：
Chuanyu Wei;Wenju Wang;W. Pang;Mingyao Meng;Lihong Jiang;Shan Xue;Yanhua Xie;Ruhong Li;
中科院分区：
文献类型：
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作者：
Chuanyu Wei;Wenju Wang;W. Pang;Mingyao Meng;Lihong Jiang;Shan Xue;Yanhua Xie;Ruhong Li;
产生烟碱诱导的杀伤（CIK）细胞是一种新兴的方法，过继供体淋巴细胞输注的患者与广泛的肿瘤。然而，我们前期的体外研究表明，CIK细胞对肺癌的杀伤效果低于其他肿瘤细胞，但其机制尚不清楚。探讨提高CIK细胞对肺癌细胞杀伤活性的可行性。白细胞介素（IL）-15是一种多效性细胞因子，其刺激NK细胞的细胞溶解活性和细胞因子分泌，这可增强CIK细胞的细胞毒活性。本研究采用IL-2联合IL-15刺激CIK细胞扩增，以增强其对肺癌细胞的杀伤作用。观察IL-2或IL-2和IL-15联合诱导的CIK细胞的表型，并评价IL-2和IL-15联合诱导的CIK细胞对肺腺癌的体内外杀伤作用。用IL-2和IL-15两者刺激的CIK细胞显示出比仅用IL-2处理的CIK细胞更大的增殖潜力。IL-15诱导还驱动了CD 3 + CD 56+亚群的扩增，并显著增强了对肿瘤细胞的细胞毒性。进一步的分析表明，CIKIL-2和IL-15注射小鼠模型显示出显著的肿瘤消退和肿瘤组织中CyclinD 1的较低表达水平。本研究为CIKIL-2和IL-15增强细胞毒作用提供了临床前证据，为肺癌患者提供了新的治疗选择。
Generation of cytokine-induced killer (CIK) cells is an emerging approach in adoptive donor lymphocyte infusion for patients with a wide range of tumors. However, our previous in vitro studies have shown that the killing efficacy of CIK cells against lung cancer was lower than other tumor cells, while the underlying mechanisms are not clear. We explored the feasibility to improve CIK cells mediated cytotoxicity against lung cancer. Interleukin (IL)-15 is a pleiotropic cytokine that stimulates cytolytic activity and cytokine secretion of NK cells, which may enhance the cytotoxic activity of CIK cells. In this study, we intended to stimulate the CIK cells by IL-2 in combination with IL-15 in cell expansion to achieve enhanced cytotoxicity against lung cancer cells. The different phenotypes of IL-2 or combination of IL-2 and IL-15 stimulated cytokine-induced killer cells were determined, and the improved cytotoxicity of IL-2 and IL-15 induced CIK cells against lung adenocarcinoma were evaluated both in vitro and in vivo. CIK cells stimulated with both IL-2 and IL-15 has shown greater proliferative potential than CIK cells treated with IL-2 alone. IL-15 induction also has driven the expansion of CD3+CD56+ subset and significantly enhanced cytotoxicity against tumor cells. Further analysis has demonstrated that CIKIL-2&IL-15injected mice models have shown significant tumor regression and lower expression level of CyclinD1 in tumor tissue. This study has provided preclinical evidences that CIKIL-2&IL-15with enhanced cytotoxicity may offer alternative treatment option for patients with lung cancer.