Chinese Academy of Sciences (CAS) Key Laboratory for Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Guangdong-Hong Kong-Macao Joint Laboratory of Human-Machine Intelligence-Synergy Systems, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Front Immunol. 2021 Aug 19;12:712936. doi: 10.3389/fimmu.2021.712936. eCollection 2021.
The engineered "obligate" anaerobic strain YB1 shows a prominent ability to repress tumor growth and metastasis, which has great potential as a novel cancer immunotherapy. However, the antitumor mechanism of YB1 remains unelucidated. To resolve the proteome dynamics induced by the engineered bacteria, we applied tumor temporal proteome profiling on murine bladder tumors after intravenous injection of either YB1 or PBS as a negative control. Our data suggests that during the two weeks treatment of YB1 injections, the cured tumors experienced three distinct phases of the immune response. Two days after injection, the innate immune response was activated, particularly the complement and blood coagulation pathways. In the meantime, the phagocytosis was initiated. The professional phagocytes such as macrophages and neutrophils were recruited, especially the infiltration of iNOS and CD68 cells was enhanced. Seven days after injection, substantial amount of T cells was observed at the invasion margin of the tumor. As a result, the tumor shrunk significantly. Overall, the temporal proteome profiling can systematically reveal the YB1 induced immune responses in tumor, showing great promise for elucidating the mechanism of bacteria-mediated cancer immunotherapy.
经工程改造的“专性”厌氧菌株 YB1 表现出显著的抑制肿瘤生长和转移的能力,有望成为一种新型的癌症免疫疗法。然而,YB1 的抗肿瘤机制尚不清楚。为了研究工程细菌诱导的蛋白质组动态变化,我们在静脉注射 YB1 或 PBS(阴性对照)后,对小鼠膀胱癌进行了肿瘤时间蛋白质组谱分析。我们的数据表明,在 YB1 注射治疗的两周内,治愈的肿瘤经历了三个不同阶段的免疫反应。注射后两天,先天免疫反应被激活,特别是补体和血液凝固途径。同时,吞噬作用被启动。专业吞噬细胞,如巨噬细胞和中性粒细胞被招募,特别是 iNOS 和 CD68 细胞的浸润增强。注射后 7 天,在肿瘤的侵袭边缘观察到大量的 T 细胞。结果,肿瘤明显缩小。总的来说,时间蛋白质组谱分析可以系统地揭示 YB1 在肿瘤中诱导的免疫反应,为阐明细菌介导的癌症免疫疗法的机制提供了很大的希望。