Targeting M-MDSCs enhances the therapeutic effect of BNCT in the 4-NQO-induced murine head and neck squamous cell carcinoma model
PurposeMalignant head and neck squamous cell carcinoma (HNSCC) is characterized by a poor prognosis and resistance to conventional radiotherapy. Infiltrating myeloid-derived suppressive cells (MDSCs) is prominent in HNSCC and is linked to immune suppression and tumor aggressiveness. This study aimed...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1263873/full |
| _version_ | 1797662472243511296 |
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| author | Chun-Hsiang Chang Chi-Jui Chen Ching-Fang Yu Ching-Fang Yu Hui-Yu Tsai Fang-Hsin Chen Chi-Shiun Chiang Chi-Shiun Chiang |
| author_facet | Chun-Hsiang Chang Chi-Jui Chen Ching-Fang Yu Ching-Fang Yu Hui-Yu Tsai Fang-Hsin Chen Chi-Shiun Chiang Chi-Shiun Chiang |
| author_sort | Chun-Hsiang Chang |
| collection | DOAJ |
| description | PurposeMalignant head and neck squamous cell carcinoma (HNSCC) is characterized by a poor prognosis and resistance to conventional radiotherapy. Infiltrating myeloid-derived suppressive cells (MDSCs) is prominent in HNSCC and is linked to immune suppression and tumor aggressiveness. This study aimed to investigate the impact of boron neutron capture therapy (BNCT) on the MDSCs in the tumor microenvironment and peripheral blood and to explore the potential for MDSCs depletion combined with BNCT to reactivate antitumor immunity.Methods and materialsCarcinogen, 4-NQO, -induced oral tumors were irradiated with a total physical dose of 2 Gy BNCT in Tsing Hua Open Reactor (THOR). Flow cytometry and immunohistochemistry accessed the dynamics of peripheral MDSCs and infiltrated MDSCs within the tumor microenvironment. Mice were injected with an inhibitor of CSF-1 receptor (CSF-1R), PLX3397, to determine whether modulating M-MDSCs could affect mice survival after BNCT.ResultsPeripheral CD11b+Ly6ChighLy6G- monocytic-MDSCs (M-MDSCs), but not CD11b+Ly6CloLy6Ghigh polymorphonuclear-MDSCs (PMN-MDSCs), increased as tumor progression. After BNCT treatment, there were temporarily decreased and persistent increases of M-MDSCs thereafter, either in peripheral blood or in tumors. The administration of PLX-3397 hindered BNCT-caused M-MDSCs infiltration, prolonged mice survival, and activated tumor immunity by decreasing tumor-associated macrophages (TAMs) and increasing CD8+ T cells.ConclusionM-MDSCs were recruited into 4-NQO-induced tumors after BNCT, and their number was also increased in peripheral blood. Assessment of M-MDSCs levels in peripheral blood could be an index to determine the optimal intervention window. Their temporal alteration suggests an association with tumor recurrence after BNCT, making M-MDSCs a potential intervention target. Our preliminary results showed that PLX-3397 had strong M-MDSCs, TAMs, and TIL (tumor-infiltrating lymphocyte) modulating effects that could synergize tumor control when combined with BNCT. |
| first_indexed | 2024-03-11T19:00:39Z |
| format | Article |
| id | doaj.art-a3828a4d2e944b0a9f2d6b1d48331b54 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-11T19:00:39Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-a3828a4d2e944b0a9f2d6b1d48331b542023-10-10T13:18:56ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-10-011310.3389/fonc.2023.12638731263873Targeting M-MDSCs enhances the therapeutic effect of BNCT in the 4-NQO-induced murine head and neck squamous cell carcinoma modelChun-Hsiang Chang0Chi-Jui Chen1Ching-Fang Yu2Ching-Fang Yu3Hui-Yu Tsai4Fang-Hsin Chen5Chi-Shiun Chiang6Chi-Shiun Chiang7Department of Biomedical Engineering and Environment Sciences, National Tsing Hua University, Hsinchu, TaiwanDepartment of Biomedical Engineering and Environment Sciences, National Tsing Hua University, Hsinchu, TaiwanInstitute for Radiological Research, Chang Gung University, Taoyuan, TaiwanDepartment of Radiation Oncology, Chang Gung Memorial Hospital Linkou Branch, Taoyuan, TaiwanInstitute of Nuclear Engineering and Science, National Tsing Hua University, Hsinchu, TaiwanInstitute of Nuclear Engineering and Science, National Tsing Hua University, Hsinchu, TaiwanDepartment of Biomedical Engineering and Environment Sciences, National Tsing Hua University, Hsinchu, TaiwanInstitute of Nuclear Engineering and Science, National Tsing Hua University, Hsinchu, TaiwanPurposeMalignant head and neck squamous cell carcinoma (HNSCC) is characterized by a poor prognosis and resistance to conventional radiotherapy. Infiltrating myeloid-derived suppressive cells (MDSCs) is prominent in HNSCC and is linked to immune suppression and tumor aggressiveness. This study aimed to investigate the impact of boron neutron capture therapy (BNCT) on the MDSCs in the tumor microenvironment and peripheral blood and to explore the potential for MDSCs depletion combined with BNCT to reactivate antitumor immunity.Methods and materialsCarcinogen, 4-NQO, -induced oral tumors were irradiated with a total physical dose of 2 Gy BNCT in Tsing Hua Open Reactor (THOR). Flow cytometry and immunohistochemistry accessed the dynamics of peripheral MDSCs and infiltrated MDSCs within the tumor microenvironment. Mice were injected with an inhibitor of CSF-1 receptor (CSF-1R), PLX3397, to determine whether modulating M-MDSCs could affect mice survival after BNCT.ResultsPeripheral CD11b+Ly6ChighLy6G- monocytic-MDSCs (M-MDSCs), but not CD11b+Ly6CloLy6Ghigh polymorphonuclear-MDSCs (PMN-MDSCs), increased as tumor progression. After BNCT treatment, there were temporarily decreased and persistent increases of M-MDSCs thereafter, either in peripheral blood or in tumors. The administration of PLX-3397 hindered BNCT-caused M-MDSCs infiltration, prolonged mice survival, and activated tumor immunity by decreasing tumor-associated macrophages (TAMs) and increasing CD8+ T cells.ConclusionM-MDSCs were recruited into 4-NQO-induced tumors after BNCT, and their number was also increased in peripheral blood. Assessment of M-MDSCs levels in peripheral blood could be an index to determine the optimal intervention window. Their temporal alteration suggests an association with tumor recurrence after BNCT, making M-MDSCs a potential intervention target. Our preliminary results showed that PLX-3397 had strong M-MDSCs, TAMs, and TIL (tumor-infiltrating lymphocyte) modulating effects that could synergize tumor control when combined with BNCT.https://www.frontiersin.org/articles/10.3389/fonc.2023.1263873/fullBNCTMDSCs4-NQOCSF-1R inhibitorHNSCC |
| spellingShingle | Chun-Hsiang Chang Chi-Jui Chen Ching-Fang Yu Ching-Fang Yu Hui-Yu Tsai Fang-Hsin Chen Chi-Shiun Chiang Chi-Shiun Chiang Targeting M-MDSCs enhances the therapeutic effect of BNCT in the 4-NQO-induced murine head and neck squamous cell carcinoma model Frontiers in Oncology BNCT MDSCs 4-NQO CSF-1R inhibitor HNSCC |
| title | Targeting M-MDSCs enhances the therapeutic effect of BNCT in the 4-NQO-induced murine head and neck squamous cell carcinoma model |
| title_full | Targeting M-MDSCs enhances the therapeutic effect of BNCT in the 4-NQO-induced murine head and neck squamous cell carcinoma model |
| title_fullStr | Targeting M-MDSCs enhances the therapeutic effect of BNCT in the 4-NQO-induced murine head and neck squamous cell carcinoma model |
| title_full_unstemmed | Targeting M-MDSCs enhances the therapeutic effect of BNCT in the 4-NQO-induced murine head and neck squamous cell carcinoma model |
| title_short | Targeting M-MDSCs enhances the therapeutic effect of BNCT in the 4-NQO-induced murine head and neck squamous cell carcinoma model |
| title_sort | targeting m mdscs enhances the therapeutic effect of bnct in the 4 nqo induced murine head and neck squamous cell carcinoma model |
| topic | BNCT MDSCs 4-NQO CSF-1R inhibitor HNSCC |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1263873/full |
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