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  

Anti-tumor effect and impact on tumor immune microenvironment of tumor-targeted Salmonella VNP20009

作　　者：韩雨衡 来兴欢 乐子薇 华子春[1] 

机构地区：[1]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

出　　处：《药学学报》2016年第9期1417-1422,共6页Acta Pharmaceutica Sinica

基　　金：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)

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。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 CD1 lb＋ monocytes within tumor tissue by raising the level of immune response and thus, induce the production of tumor necrosis factor- a （TNF-a） and interferon-v （IFN-v） to kill tumor cells bv breakin~ the immuno-evasion barrier in the tumor microenvironment.

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 

分 类 号：R965[医药卫生—药理学]