肿瘤局部复发是影响口腔鳞癌预后的重要因素，其发生机制仍有待进一步阐明。前期我们发现删除肿瘤相关巨噬细胞（TAMs）可抑制口腔鳞癌的进程（J Dent Res.2019,98:896-903），后续研究发现：衰老期TAMs可促进口腔癌干细胞从休眠状态进入活跃的增殖阶段。藉此创新性提出“衰老期TAMs可能“唤醒”口腔休眠癌干细胞进而驱动肿瘤发生”的科学假说。本项目拟联合采用免疫荧光、流式分选、蛋白转导、复合移植瘤模型等技术，研究①口腔癌干细胞肿瘤模型中TAMs的衰老特性；②衰老期TAMs是否可“唤醒”口腔休眠癌干细胞；③衰老期TAMs是否通过TGF-β/PI3K调控口腔癌干细胞休眠-苏醒平衡；④靶向干预衰老期TAMs是否对口腔休眠癌干细胞肿瘤发生有阻抑效应。本项目对探索口腔鳞癌局部复发的新机制、制订有效抑制复发的新策略具有重要的理论意义和应用价值。

Tumor local recurrence acts as one of the main factors affecting the prognosis of oral squamous cell carcinomas (OSCCs), however, its potential mechanism still remains largely unknown. In the previous study, we have demonstrated that tumor associated macrophages (TAMs) ablation could inhibit the progression of OSCCs (J Dent Res. 2019, 98: 896-903). Follow-up studies have found that the senescent macrophages promoted the cancer stem cells (CSCs) from dormancy to out-of-dormancy exhibiting with active proliferation. Therefore, the applicant proposes the new hypothesis that senescent TAMs might awake the oral resting CSCs into out-of-dormancy, subsequently leading to tumorigenesis. This project will apply immunofluorescence, flow cell sorting, protein transduction, tumor transplant and so on to investigate that: ①the characters of senescent TAMs in CSCs tumor-bearing model; ②if the senescent TAMs can awake oral resting CSCs; ③if the senescent TAMs regulate the balance between dormancy and out-of-dormancy of CSCs via TGF-β/PI3K pathway; ④if the targeted senescent TAMs can block the tumorigenesis and/or progression in OSCCs derived from resting CSCs. This study possesses important theoretical and application value to understand the novel mechanism of tumor local recurrence in OSCCs, paving the way for suppressing tumor local recurrence by effective strategies.