用K-ras突变肽脉冲的树突状细胞增强细胞因子诱导的杀伤细胞对胰腺癌的治疗效果。

The therapeutic effect of cytokine-induced killer cells on pancreatic cancer enhanced by dendritic cells pulsed with K-ras mutant peptide.

作者信息

Tan Guang, Zhang Xin, Feng Hongbo, Luo Haifeng, Wang Zhongyu

机构信息

Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, No. 222, Zhongshan Road, Dalian 116011, China.

出版信息

Clin Dev Immunol. 2011;2011:649359. doi: 10.1155/2011/649359. Epub 2011 Oct 19.

OBJECTIVE

This study is to investigate the role of the CIKs cocultured with K-ras-DCs in killing of pancreatic cancer cell lines, PANC-1 (K-ras(+)) and SW1990 (K-ras(-)).

METHODS

CIKs induced by IFN-γ, IL-2, and anti-CD3 monoantibody, K-ras-DCCIKs obtained by cocultivation of k-ras-DCs and CIKs. Surface markers examined by FACS. IFN-γ IL-12 ,CCL19 and CCL22 detected by ELISA. Proliferation of various CIKs tested via 3H-TdR. Killing activities of k-ras-DCCIKs and CTLs examined with 125IUdR.

RESULTS

CD3(+)CD56(+) and CD3(+)CD8(+) were highly expressed by K-ras-DCCIKs. In its supernatant, IFN-γ, IL-12, CCL19 and CCL22 were significantly higher than those in DCCIK and CIK. The killing rate of K-ras-DCCIK was greater than those of CIK and CTL. CTL induced by K-ras-DCs only inhibited the PANC-1 cells.

CONCLUSIONS

The k-ras-DC can enhance CIK's proliferation and increase the killing effect on pancreatic cancer cell. The CTLs induced by K-ras-DC can only inhibit PANC-1 cells. In this study, K-ras-DCCIKs also show the specific inhibition to PANC-1 cells, their tumor suppression is almost same with the CTLs, their total tumor inhibitory efficiency is higher than that of the CTLs.

目的

本研究旨在探讨与K-ras基因修饰树突状细胞（K-ras-DCs）共培养的细胞因子诱导的杀伤细胞（CIKs）对胰腺癌细胞系PANC-1（K-ras(+)）和SW1990（K-ras(-)）的杀伤作用。

方法

用γ干扰素、白细胞介素-2和抗CD3单克隆抗体诱导CIKs，通过K-ras-DCs与CIKs共培养获得K-ras-DC-CIKs。用流式细胞术检测表面标志物。用酶联免疫吸附测定法检测γ干扰素、白细胞介素-12、CCL19和CCL22。通过3H-胸腺嘧啶核苷检测各种CIKs的增殖情况。用125I-尿嘧啶核苷检测K-ras-DC-CIKs和细胞毒性T淋巴细胞（CTLs）的杀伤活性。

结果

K-ras-DC-CIKs高表达CD3(+)CD56(+)和CD3(+)CD8(+)。其培养上清中，γ干扰素、白细胞介素-12、CCL19和CCL22显著高于树突状细胞-细胞因子诱导的杀伤细胞（DCCIK）和CIK。K-ras-DC-CIK的杀伤率高于CIK和CTL。K-ras-DCs诱导的CTL仅抑制PANC-1细胞。