论文部分内容阅读
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 facultative anaerobic gram-negative bacterium that targets tumor tissue and grows and reproduces, showing significant antitumor effects. The attenuated Salmonella strain VNP20009 is obtained by knocking out virulence genes on the basis of Salmonella typhimurium and has the advantages of good curative effect and low toxic and side effects. The immune microenvironment in the tumor is immunosuppressive, making it difficult for immune cells to kill tumor cells. One of the anti-tumor effects of VNP20009 is to attack the tumor by increasing the body’s immune response. This study used VNP20009 strain to treat B16F10 mouse subcutaneous melanoma model to explore the mechanism of VNP20009 in the treatment of tumors. The results showed that VNP20009 can effectively inhibit tumor growth and promote tumor cell necrosis and apoptosis. Further study found that VNP20009 can increase the proportion of CD8 ~ + T cells and CD11b ~ + monocytes - macrophages in tumor by increasing the level of immune response in tumor and inducing the production of tumor necrosis factor-α (TNF-α) and Interferon-γ (IFN-γ), the destruction of immune escape within the environment, resulting in anti-tumor effect.