Yang Xin-Jing, Huang Jian-An, Lei Wei, Zhu Yi-Bei, Zhang Xue-Guang
Department of Respiratory Medicine, The First Affiliated Hospital, Soochow University, Suzhou, Jiangsu, 215006, P. R. China.
Ai Zheng. 2006 Nov;25(11):1329-33.
BACKGROUND & OBJECTIVE: Cytokine-induced killer (CIK) cells have high cytotoxic activity against tumor cells. Dendritic cells (DCs) are the strongest antigen-presenting cells (APC) and could increase the cytotoxic activity of immunologic effector cells against tumor cells. This study was to investigate the changes of phenotype, proliferative activity, and in vitro and in vivo cytotoxicity of CIK cells after in vitro co-culturing with DCs.
DCs and CIK cells were prepared routinely from human peripheral blood mononuclear cells (PBMC), then CIK cells were cocultured with autologous DCs for 5 days at a stimulator-to-responder ratio of 1:10 to prepare immunologic effector DC-CIK cells. Phenotypes of DC-CIK cells were analyzed by flow cytometry; The in vitro cytotoxicity of DC-CIK cells was detected by 3H-TdR incorporation method; the in vivo antitumor activity was evaluated in BALB/c nude mice bearing A549 lung cancer.
At the 14th day of culture, compared with CIK cells, DC-CIK cells got a significant increase of proliferation rate [(17.0+/-1.8) times vs. (10.9+/-2.0) times, P<0.05] and CD3+CD56+ expression rate [(36.0+/-4.2)% vs. (25.7+/-2.9)%, P<0.05], and resulted in an enhancement of cytotoxicity to A549 cells (P<0.05) in vivo. At the 51st day after inoculation of tumor cells, the inhibition rate was significantly higher in DC-CIK group than in CIK group (62.9% vs. 41.5%, P<0.05). DC-CIK cells and CIK cells showed significant inhibitory effects on the growth of transplanted tumor cells as compared with control group (P<0.01).
DC-CIK cells have higher proliferative activity and cytotoxicity in vitro and in vivo against lung cancer in comparison with CIK cells alone.
细胞因子诱导的杀伤细胞(CIK)对肿瘤细胞具有高细胞毒性活性。树突状细胞(DC)是最强的抗原呈递细胞(APC),可增强免疫效应细胞对肿瘤细胞的细胞毒性活性。本研究旨在探讨CIK细胞与DC体外共培养后其表型、增殖活性及体外和体内细胞毒性的变化。
常规从人外周血单个核细胞(PBMC)制备DC和CIK细胞,然后将CIK细胞与自体DC以1:10的刺激细胞与反应细胞比例共培养5天,制备免疫效应细胞DC-CIK细胞。采用流式细胞术分析DC-CIK细胞的表型;采用3H-TdR掺入法检测DC-CIK细胞的体外细胞毒性;在荷A549肺癌的BALB/c裸鼠中评估其体内抗肿瘤活性。
培养第14天,与CIK细胞相比,DC-CIK细胞的增殖率显著提高[(17.0±1.8)倍对(10.9±2.0)倍,P<0.05],CD3+CD56+表达率显著提高[(36.0±4.2)%对(25.7±2.9)%,P<0.05],并导致体内对A549细胞的细胞毒性增强(P<0.05)。接种肿瘤细胞后第51天,DC-CIK组的抑制率显著高于CIK组(62.9%对41.5%,P<0.05)。与对照组相比,DC-CIK细胞和CIK细胞对移植肿瘤细胞的生长均显示出显著的抑制作用(P<0.01)。
与单独的CIK细胞相比,DC-CIK细胞在体外和体内对肺癌具有更高的增殖活性和细胞毒性。