Synergistic Antitumor Effect of Combined Radiotherapy and Engineered <i>Salmonella typhimurium</i> in an Intracranial Sarcoma Mouse Model
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 <i>Salmon...
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MDPI AG
2023-07-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/11/7/1275 |
| _version_ | 1797587325867261952 |
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| author | Zhipeng Liu Sa-Hoe Lim Jung-Joon Min Shin Jung |
| author_facet | Zhipeng Liu Sa-Hoe Lim Jung-Joon Min Shin Jung |
| author_sort | Zhipeng Liu |
| collection | DOAJ |
| description | 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 <i>Salmonella typhimurium</i> 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<sup>+</sup> 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<sup>+</sup> 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. |
| first_indexed | 2024-03-11T00:34:33Z |
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| id | doaj.art-c42e28b387914555a5abd84f2d55b6ed |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-11T00:34:33Z |
| publishDate | 2023-07-01 |
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| spelling | doaj.art-c42e28b387914555a5abd84f2d55b6ed2023-11-18T21:42:05ZengMDPI AGVaccines2076-393X2023-07-01117127510.3390/vaccines11071275Synergistic Antitumor Effect of Combined Radiotherapy and Engineered <i>Salmonella typhimurium</i> in an Intracranial Sarcoma Mouse ModelZhipeng Liu0Sa-Hoe Lim1Jung-Joon Min2Shin Jung3Brain Tumor Research Laboratory, Biomedical Research Institute, Chonnam National University Hwasun Hospital, Gwangju 58128, Republic of KoreaBrain Tumor Research Laboratory, Biomedical Research Institute, Chonnam National University Hwasun Hospital, Gwangju 58128, Republic of KoreaDepartment of Nuclear Medicine, Institute for Molecular Imaging and Theranostics, Chonnam National University Medical School, Hwasun Hospital, 322 Seoyang-ro, Gwangju 58128, Republic of KoreaBrain Tumor Research Laboratory, Biomedical Research Institute, Chonnam National University Hwasun Hospital, Gwangju 58128, Republic of KoreaIntracranial 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 <i>Salmonella typhimurium</i> 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<sup>+</sup> 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<sup>+</sup> 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.https://www.mdpi.com/2076-393X/11/7/1275radiotherapyimmunotherapy<i>Salmonella typhimurium</i>intracranial sarcomaadjuvantneoadjuvant |
| spellingShingle | Zhipeng Liu Sa-Hoe Lim Jung-Joon Min Shin Jung Synergistic Antitumor Effect of Combined Radiotherapy and Engineered <i>Salmonella typhimurium</i> in an Intracranial Sarcoma Mouse Model Vaccines radiotherapy immunotherapy <i>Salmonella typhimurium</i> intracranial sarcoma adjuvant neoadjuvant |
| title | Synergistic Antitumor Effect of Combined Radiotherapy and Engineered <i>Salmonella typhimurium</i> in an Intracranial Sarcoma Mouse Model |
| title_full | Synergistic Antitumor Effect of Combined Radiotherapy and Engineered <i>Salmonella typhimurium</i> in an Intracranial Sarcoma Mouse Model |
| title_fullStr | Synergistic Antitumor Effect of Combined Radiotherapy and Engineered <i>Salmonella typhimurium</i> in an Intracranial Sarcoma Mouse Model |
| title_full_unstemmed | Synergistic Antitumor Effect of Combined Radiotherapy and Engineered <i>Salmonella typhimurium</i> in an Intracranial Sarcoma Mouse Model |
| title_short | Synergistic Antitumor Effect of Combined Radiotherapy and Engineered <i>Salmonella typhimurium</i> in an Intracranial Sarcoma Mouse Model |
| title_sort | synergistic antitumor effect of combined radiotherapy and engineered i salmonella typhimurium i in an intracranial sarcoma mouse model |
| topic | radiotherapy immunotherapy <i>Salmonella typhimurium</i> intracranial sarcoma adjuvant neoadjuvant |
| url | https://www.mdpi.com/2076-393X/11/7/1275 |
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