Abstract
Head and neck squamous cell carcinoma (HNSCC) is the 7th leading cancer worldwide, and current treatments, such as surgery, radiation, chemotherapy, targeted therapy, and immunotherapy, have not produced satisfactory results. Boron neutron capture therapy (BNCT) is an emerging treatment modality that targets tumors while sparing normal tissue, based on the difference in uptake of boron10-containing drugs. While it has shown encouraging outcomes in various disease sites, there is still a lack of information on the immune profiles found in the tumor microenvironment and its association with immune subsets in peripheral circulation after BNCT. In this study, a murine oral squamous cell carcinoma (OSCC) was established by intake of 4-nitroquinolone-1-oxide (4-NQO) carcinogen, and tumor-bearing mice were allocated to either the untreated, conventional 6 Gy RT (CON-RT) or BNCT group. Peripheral blood was collected before treatment and then again at days 1, 3, and 7 post-irradiation to analyze the immune profiles. Tumor samples were also collected on day 7 post-irradiation to examine the changes in the tumor microenvironment. One day after irradiation, no matter RT or BNCT, monocytic myeloid-derived suppressor cells (M-MDSCs), but not granulocytic MDSCs (G-MDSCs), decrease significantly despite no apparent change in tumor size. Significant tumor control was noticed on day 3 and day 7 post-irradiation, but the peripheral blood had a substantial rise in the number of G-MDSC and M-MDSCs following CON-RT and BNCT, respectively. Immediately drop of CD8 T cells on day 1 post-irradiation was also found after exposure to both CON-RT and BNCT and remained after that. The decline of CD4 T cells was also noticed after exposure to either CON-RT or BNCT, but the number rebounded significantly in the CON-RT group on day 7. BNCT was more effective in controlling the tumor but resulted in a tumor microenvironment with higher vascular density and increased MDSC subsets infiltration into OSCC tumors compared to CON-RT. This study showed that BNCT induces better tumor control but a more immunosuppressive tumor microenvironment than CON-RT. The changes in immune profiles in peripheral blood were in accord with those in the tumor microenvironment in response to BNCT and photon irradiation. They could serve as an indicator of the treatment response following different radiation treatment protocols. Combining BNCT with MDSC-targeting may be a potential strategy to improve treatment efficacy further and is currently being investigated.