目的: 探讨粪菌移植(fecal microbiota transplantation, FMT)能否提高抗程序性细胞死亡蛋白1 (anti-programmed cell death protein 1, PD-1)疗法治疗卵巢癌荷瘤小鼠的效果及可能的作用机制。方法: 随机将20只5周龄的C57bl/6 SPF雌鼠分为4组,每组5只,分别为对照组(NC组)、FMT组、PD-1组、联合治疗(FMT联合PD-1)组。每组小鼠予广谱抗生素统一处理2周,构建假无菌小鼠模型。第0天,腹腔注射ID8-luc细胞,构建卵巢癌荷瘤小鼠模型。在药物治疗前后,分别给小鼠进行1次动物活体成像(in-vivo imaging system, IVIS),评价治疗效果。第30天即实验结束后,小鼠脱颈处死,取腹膜肿瘤组织进行HE和免疫组化染色,观察肿瘤组织病理变化。结果: 联合治疗组比PD-1组治疗卵巢癌荷瘤小鼠效果更好,并且降低了肿瘤细胞PD-L1表达(P＜0.05)和增加了肿瘤微环境(the tumor microenvironment, TME)中CD8+T细胞浸润(P＜0.05)。结论: FMT通过增加肿瘤微环境中CD8+T细胞的浸润来提高PD-1单抗治疗卵巢癌荷瘤小鼠的效果。
Objective: To investigate whether intestinal fecal microbiota transplantation (FMT) can improve the efficacy of anti-programmed cell death protein 1 (PD-1) therapy in the treatment of ovarian cancer and its possible mechanisms of action. Methods: Twenty 5-week-old C57bl/6 SPF female mice were randomly divided into four groups, with five mice in each group, namely the control group (NC group), fecal bacteria transplantation FMT group, PD-1 group, and the combined treatment group (FMT combined with PD-1 group). Each group of mice was uniformly treated with broad-spectrum antibiotics for 2 weeks to construct a pseudo sterile mouse model. On day 0, ID8-luc cells were injected intraperitoneally to construct an ovarian cancer bearing mouse model. Before medication and 2 weeks after medication treatment, mice were subjected to one in vivo imaging system (IVIS) to evaluate the therapeutic effect. After the end of the experiment on the 30th day, the mice were decapitated and killed. Peritoneal tumor tissue was taken for HE and immunohistochemical staining to observe the pathological changes of the tumor tissue. Results: The combined treatment group was better than the single PD-1 group in treating ovarian cancer bearing mice, and reduced the expression of PD-L1 in tumor cells (P＜0.05),and increased the infiltration of CD8+T cells in the tumor microenvironment (TME) (P＜0.05). Conclusion: Fecal microbiota transplantation (FMT) enhances the efficacy of PD-1 monoclonal antibody in treating ovarian cancer bearing mice by increasing the infiltration of CD8+T cells in the tumor microenvironment (TME).
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