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工程学通过增强细胞毒性T细胞反应提高抗肿瘤疗效。

Engineering improves antitumor efficacy via enhancing cytotoxic T cell responses.

作者信息

Zhang Hong, Luo Yinlin, Zhao Xincheng, Liu Xiande

机构信息

Institute of Tropical Agriculture and Forestry, Hainan University, Haikou, Hainan 570228, P.R. China.

College of Animal Science and Technology, Anhui Agricultural University, Heifei, Anhui 230036, P.R. China.

出版信息

Mol Ther Oncol. 2024 Feb 7;32(1):200770. doi: 10.1016/j.omton.2024.200770. eCollection 2024 Mar 21.

Abstract

Cancer immunotherapy based on bioengineering of bacteria can effectively increase anticancer immune responses. However, few studies have investigated the antitumor potential of engineering . Here, we genetically engineered to overexpress flagellin B (FlaB) protein in a murine CT26 tumor model. We found that a large number of FlaB-expressing colonized tumor tissues, enhanced T cell infiltration and secretion of cytokines and cytotoxic proteins in tumors, and significantly restrained tumor growth. Our results also showed that programmed death ligand 1 (PD-L1) expression in tumor-infiltrating immune cells was elevated after treatment with FlaB-expressing . In addition, combination therapy with FlaB-expressing and PD-L1 blockade synergistically improved antitumor efficacy by enhancing infiltration of CD8 cells. Furthermore, serum liver biochemical indices of mice increased in the short term in both the and the FlaB-expressing treatment groups but gradually recovered in the later stage of treatment so that FlaB protein expression did not increase the toxicity of . Taken together, our results suggest that could serve as an engineered bacterium for bacterium-based cancer immunotherapy.

摘要

基于细菌生物工程的癌症免疫疗法可有效增强抗癌免疫反应。然而,很少有研究调查工程菌的抗肿瘤潜力。在此,我们在小鼠CT26肿瘤模型中对细菌进行基因工程改造,使其过表达鞭毛蛋白B(FlaB)。我们发现,大量表达FlaB的细菌定殖于肿瘤组织,增强了肿瘤内T细胞浸润以及细胞因子和细胞毒性蛋白的分泌,并显著抑制了肿瘤生长。我们的结果还表明,用表达FlaB的细菌处理后,肿瘤浸润免疫细胞中程序性死亡配体1(PD-L1)的表达升高。此外,表达FlaB的细菌与PD-L1阻断剂联合治疗通过增强CD8细胞浸润,协同提高了抗肿瘤疗效。此外,在细菌治疗组和表达FlaB的细菌治疗组中,小鼠血清肝脏生化指标在短期内均有所升高,但在治疗后期逐渐恢复,因此FlaB蛋白表达并未增加细菌的毒性。综上所述,我们的结果表明,该细菌可作为基于细菌的癌症免疫疗法的工程菌。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b3b/10937320/8a931fa90a5c/fx1.jpg

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