树突状细胞诱导的LAK细胞对肺癌的生长抑制作用

Inhibitive effect of LAK cells induced by dendritic cells on implanted lung cancer in nude mice

目的 研究肺癌细胞裂解物负载的树突状细胞 (DC)诱导的淋巴因子激活杀伤细胞 (LAK )对肺腺癌裸鼠移植瘤的生长抑制作用。方法 肺腺癌患者手术切除标本接种裸鼠皮下建立肺腺癌移植瘤模型 ,同时将手术切除标本用反复冻融的方法制备肿瘤细胞裂解物 ;同一患者外周血分离得到的单个核细胞中 ,贴壁的细胞加入DC生长因子 (DCGF)培养得DC ,未贴壁的细胞加入rhIL 2培养得LAK细胞。用肿瘤细胞裂解物负载自体DC ,诱导LAK细胞生成DC LAK细胞 ,注射荷瘤裸鼠腋下以观察DC LAK细胞对肺癌移植瘤的生长抑制作用。结果 用肺癌手术标本能成功建立裸鼠移植瘤模型。DC LAK组、LAK组、DC组和生理盐水对照组肿瘤瘤重平均值分别为 0 .47、1.0 5、1.3 0和 1.5 8g ,DC LAK组、LAK组和DC组肿瘤生长抑制率分别为 70 .3 %、3 3 .5 %和 17.9% ,DC LAK细胞具有抑制裸鼠肺癌移植瘤生长的作用而且强于LAK细胞 (P <0 .0 5 )。结论 通过荷瘤裸鼠体内抗瘤实验证实了DC LAK细胞的抗肺癌作用明显高于LAK细胞 ,提示DC LAK细胞治疗是更为有效的抗肺癌生物治疗方法 。

Objective To study the inhibitive effect of LAK cells induced by dendritic cells (DCs) on implanted lung adenocarcinoma in nude mice. Methods The lung adenocarcinoma model was constructed in nude mice using the resected samples of lung cancer patient. The lung cancer cell lysate was obtained by free-zing and thrawing cycles. Peripheral blood mononuclear cells (PBMNC) were obtained from venous blood of the same patient, in which the adherent PBMNC fraction was cultured with DCGF, and the non-adherent PBMNC fraction was cultured with rhIL-2. DCs were pulsed with lung cancer cell lysates. And then mature DCs were incubated with LAK cells and the mixed cells were named DC-LAK cells. DC-LAK cells were injected into lung cancer-bearing nude mice to observe the inhibitive effect. Results The lung adenocarcinoma mo-del was successfully constructed. The average tumor weights of DC-LAK, LAK, DC and saline control groups were 0.47, 1.05, 1.30 and 1.58 g respectively, and the inhibitive rates of DC-LAK, LAK and DC were 70.3%, 33.5% and 17.9% respectively. The antitumor activity of DC-LAK cells was significantly stronger than that of LAK cells (P<0.05). Conclusion The results of in vivo experiment show that the antitumor activity of DC-LAK cells is stronger than that of LAK cells, so DC-LAK cells treatment may be a more efficient approach of lung cancer biological therapy. This experiment may provide a foundation for clinical application of DC vaccine.