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经脂多糖刺激的辐照肿瘤细胞可引发增强的抗肿瘤免疫力。

Irradiated tumor cells of lipopolysaccharide stimulation elicit an enhanced anti-tumor immunity.

作者信息

Li Yuli, Shen Guobo, Nie Wen, Li Zhimian, Sang Yaxiong, Zhang Binglan, Wei Yuquan

机构信息

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Gaopeng Street, Keyuan Road 4, Chengdu, 610041, Sichuan, People's Republic of China.

出版信息

J Cancer Res Clin Oncol. 2014 Nov;140(11):1815-23. doi: 10.1007/s00432-014-1721-4. Epub 2014 Jun 14.

Abstract

PURPOSE

Lipopolysaccharide (LPS) is a major component of the outer surface membrane of Gram-negative bacteria which has been proved an effective immune enhancer. Here, we investigated the anti-tumor effect of irradiated tumor cells that stimulated by LPS in mouse xenografts models.

METHODS

Tumor cells were irradiated after stimulation with 1 μg/mL LPS for 48 h. The C57BL/6 mice were immunized subcutaneously with irradiated tumor cells. The anti-tumor effect of lymphocytes of immunized mice was investigated. The cytotoxicity of spleen lymphocytes from immunized mice was determined by a standard (51)Cr-release assay. The roles of immune cell subsets in anti-tumor activity were assessed by injected intraperitoneally with monoclonal antibodies.

RESULTS

We observed that the vaccine of irradiated tumor cell with LPS-stimulated elicited a stronger protective anti-tumor immunity than other controls. Adoptive transfer of lymphocytes of immunized mice showed that the cellular immune response was involved in the anti-tumor effect. And this effect was achieved by activation of antigen-specific CD8(+) T cell response and reduction of myeloid-derived suppressor cells (MDSCs, Gr1(+) CD11b (+) ), which were confirmed by depletion of immune cell subsets and flow cytometry analysis.

CONCLUSIONS

In summary, our study showed that stimulation of LPS was able to enhance anti-tumor immunity of vaccination with tumor cells after irradiation treatment, which might be a new strategy for cancer therapy.

摘要

目的

脂多糖(LPS)是革兰氏阴性菌外表面膜的主要成分,已被证明是一种有效的免疫增强剂。在此,我们在小鼠异种移植模型中研究了经LPS刺激的辐照肿瘤细胞的抗肿瘤作用。

方法

用1μg/mL LPS刺激肿瘤细胞48小时后进行辐照。将C57BL/6小鼠皮下注射辐照后的肿瘤细胞进行免疫。研究免疫小鼠淋巴细胞的抗肿瘤作用。通过标准的(51)Cr释放试验测定免疫小鼠脾淋巴细胞的细胞毒性。通过腹腔注射单克隆抗体评估免疫细胞亚群在抗肿瘤活性中的作用。

结果

我们观察到,经LPS刺激的辐照肿瘤细胞疫苗引发的保护性抗肿瘤免疫比其他对照组更强。免疫小鼠淋巴细胞的过继转移表明细胞免疫反应参与了抗肿瘤作用。并且这种作用是通过激活抗原特异性CD8(+)T细胞反应和减少髓系来源的抑制细胞(MDSCs,Gr1(+)CD11b(+))来实现的,这通过免疫细胞亚群的去除和流式细胞术分析得到证实。

结论

总之,我们的研究表明,LPS刺激能够增强辐照治疗后肿瘤细胞疫苗接种的抗肿瘤免疫力,这可能是一种新的癌症治疗策略。

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