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

Oncology

Chi-Jui Chen¹  Chun-Hsiang Chang¹  Chi-Shiun Chiang²  Ching-Fang Yu³  Fang-Hsin Chen⁴  Hui-Yu Tsai⁴ 

[1] Department of Biomedical Engineering and Environment Sciences, National Tsing Hua University, Hsinchu, Taiwan;Department of Biomedical Engineering and Environment Sciences, National Tsing Hua University, Hsinchu, Taiwan;Institute of Nuclear Engineering and Science, National Tsing Hua University, Hsinchu, Taiwan;Institute for Radiological Research, Chang Gung University, Taoyuan, Taiwan;Department of Radiation Oncology, Chang Gung Memorial Hospital Linkou Branch, Taoyuan, Taiwan;Institute of Nuclear Engineering and Science, National Tsing Hua University, Hsinchu, Taiwan;

关键词: BNCT;    MDSCs;    4-NQO;    CSF-1R inhibitor;    HNSCC;   

DOI  :  10.3389/fonc.2023.1263873

 received in 2023-07-20, accepted in 2023-09-15,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2023 Chang, Chen, Yu, Tsai, Chen and Chiang