M2 マクロファージは血管形成を促し放射線照射後の口腔癌再発を導く

抄録

Despite the fact that radiation is one of the standard therapies in patients with oral cancer, tumor can recur even in the early stages of the disease, negatively affecting outcomes and the quality of life. We previously found that CD11b⁺ bone marrow-derived cells (BMDCs) were recruited into human glioblastoma multiforme (GBM), leading to re-organization of the vasculature and tumour regrowth. However, it is not yet known how these cells contribute to tumour vascularization. In the present study, we investigated the role of infiltrating CD11b⁺ myeloid cells in the vascularization and recurrence of oral squamous cell carcinoma (OSCC). In a xenograft mouse model, local irradiation caused vascular damage and hypoxia in the tumor and increased infiltration of CD11b⁺ myeloid cells. These infiltrating cells showed characteristics of M2 macrophages (M2Mφs) and are associated with the promotion of vascularization. M2Mφs promoted tumor progression in recurrence after irradiation as compared with non-irradiated tumours. In addition, we found that CD11b⁺ myeloid cells, as well as CD206⁺ M2Mφs, are increased during recurrence after radiotherapy in human OSCC specimens. Our findings may lead to the development of potential clinical biomarkers or treatment targets in patients with irradiated OSCC.