药学学报, 2016, 51(9): 1417-1422
引用本文:
韩雨衡, 来兴欢, 乐子薇, 华子春. 肿瘤靶向性沙门氏菌VNP20009抗肿瘤作用及其对肿瘤免疫微环境的影响[J]. 药学学报, 2016, 51(9): 1417-1422.
HAN Yu-heng, LAI Xing-huan, LE Zi-wei, HUA Zi-chun. Anti-tumor effect and impact on tumor immune microenvironment of tumor-targeted Salmonella VNP20009[J]. Acta Pharmaceutica Sinica, 2016, 51(9): 1417-1422.

肿瘤靶向性沙门氏菌VNP20009抗肿瘤作用及其对肿瘤免疫微环境的影响
韩雨衡, 来兴欢, 乐子薇, 华子春
南京大学生命科学学院, 医药生物技术国家重点实验室, 江苏 南京 210093
摘要:
沙门氏菌是一类兼性厌氧革兰阴性菌,能够靶向肿瘤组织并生长繁殖,表现出显著的抗肿瘤效果。减毒沙门氏菌菌株VNP20009是在鼠伤寒沙门氏菌基础上敲除毒性基因得到,有治疗效果好、毒副作用低的优势。肿瘤内免疫微环境是免疫抑制的,使免疫细胞难以杀伤肿瘤细胞,而VNP20009的抗肿瘤效应之一是通过提高机体的免疫反应水平以攻击肿瘤。本研究使用VNP20009菌株治疗B16F10小鼠皮下黑色素瘤模型,以探究VNP20009治疗肿瘤的机制。结果发现,VNP20009可以有效抑制肿瘤生长,促使肿瘤细胞坏死与凋亡。进一步研究发现,VNP20009能够通过提高肿瘤内的免疫反应水平进而提高肿瘤内CD8+T细胞与CD11b+单核-巨噬细胞的比例,诱导其产生肿瘤坏死因子-α(TNF-α)与干扰素-γ(IFN-γ),破坏肿瘤内免疫逃逸的环境,产生抗肿瘤效果。
关键词:    沙门氏菌      肿瘤微环境      黑色素瘤      肿瘤浸润淋巴细胞      单核细胞      T淋巴细胞     
Anti-tumor effect and impact on tumor immune microenvironment of tumor-targeted Salmonella VNP20009
HAN Yu-heng, LAI Xing-huan, LE Zi-wei, HUA Zi-chun
The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China
Abstract:
Salmonella is a gram-negative bacterium that has an ability of tumor-targeting growth and proliferation. Attenuated Salmonella VNP20009 is a virulence genes-knockout bacterial strain based on Salmonella typhimurium, and it has an advantage of good therapeutic effect and low toxicity. One of the mechanisms of anti-tumor effect of VNP20009 is the induction of inflammatory reaction within tumor tissues. We used B16F10 melanoma model to investigate the mechanism of the anti-tumor effect of VNP20009. VNP20009 treatment effectively inhibited tumor growth and promoted the apoptosis and necrosis of tumor cells. VNP20009 increased the accumulation or infiltration of CD8+ T cells and CD11b+ monocytes within tumor tissue by raising the level of immune response and thus, induce the production of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) to kill tumor cells by breaking the immuno-evasion barrier in the tumor microenvironment.
Key words:    Salmonella    tumor microenvironment    melanoma    tumor-infiltrating lymphocyte    monocyte    T-lymphocyte   
收稿日期: 2016-05-04
DOI: 10.16438/j.0513-4870.2016-0425
基金项目: 高等学校博士学科点专项科研基金(优先发展领域)资助项目(20130091130003)。
通讯作者: 华子春
Email: huazc@nju.edu.cn
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