Liu Zhipeng, Lim Sa-Hoe, Min Jung-Joon, Jung Shin
Brain Tumor Research Laboratory, Biomedical Research Institute, Chonnam National University Hwasun Hospital, Gwangju 58128, Republic of Korea.
Department of Neurosurgery, Chonnam National University Medical School, Hwasun Hospital, 322 Seoyang-ro, Gwangju 58128, Republic of Korea.
Vaccines (Basel). 2023 Jul 23;11(7):1275. doi: 10.3390/vaccines11071275.
Intracranial sarcoma is an uncommon aggressive cancer with a poor prognosis and a high recurrence rate. Although postoperative adjuvant radiotherapy (RT) is the most recommended treatment strategy, it does not significantly improve survival rates. In this study, we used an attenuated strain engineered to secrete Vibrio vulnificus flagellin B (SLpFlaB) as an immunotherapy to assist with the antitumor effects of RT on intracranial sarcoma. In vitro, the expression of γH2AX and cleaved caspase-3 was analyzed by Western blot. In vivo detection of SLpFlaB colonization time in tumors was measured using an in vivo imaging system (IVIS). Tumor growth delay and elimination were demonstrated in an intracranial mouse model, and the distribution of macrophages, M1 macrophages, and CD8 cells after treatment was measured using FACS analysis. Our findings in vitro suggest that combination therapy increases S-180 radiosensitivity, the expression of DNA double-strand breaks, and programmed cell death. In vivo, combination treatment causes intracranial sarcoma to be eliminated without tumor recurrence and redistribution of immune cells in the brain, with data showing the enhanced migration and infiltration of CD8 T cells and macrophages, and an increased proportion of M1 macrophage polarization. Compared to RT alone, the combination therapy enhanced the radiosensitivity of S-180 cells, promoted the recruitment of immune cells at the tumor site, and prevented tumor recurrence. This combination therapy may provide a new strategy for treating intracranial sarcomas.
颅内肉瘤是一种罕见的侵袭性癌症，预后较差且复发率高。尽管术后辅助放疗（RT）是最推荐的治疗策略，但它并不能显著提高生存率。在本研究中，我们使用一种经过工程改造以分泌创伤弧菌鞭毛蛋白B（SLpFlaB）的减毒株作为免疫疗法，以辅助RT对颅内肉瘤的抗肿瘤作用。在体外，通过蛋白质免疫印迹法分析γH2AX和裂解的半胱天冬酶-3的表达。使用体内成像系统（IVIS）测量体内肿瘤中SLpFlaB的定殖时间。在颅内小鼠模型中证明了肿瘤生长延迟和消除，并使用荧光激活细胞分选（FACS）分析测量治疗后巨噬细胞、M1巨噬细胞和CD8细胞的分布。我们的体外研究结果表明，联合治疗可提高S-180放射敏感性、DNA双链断裂的表达和程序性细胞死亡。在体内，联合治疗可消除颅内肉瘤且无肿瘤复发，并且脑内免疫细胞重新分布，数据显示CD8 T细胞和巨噬细胞的迁移和浸润增强，M1巨噬细胞极化比例增加。与单独放疗相比，联合治疗增强了S-180细胞的放射敏感性，促进了肿瘤部位免疫细胞的募集，并防止了肿瘤复发。这种联合治疗可能为治疗颅内肉瘤提供一种新策略。
