口腔鳞癌严重威胁人类健康与生命，其发展不仅依赖于肿瘤细胞自身的直接作用，肿瘤微环境中免疫细胞尤其巨噬细胞的功能异常与细胞内复杂的信号转导变化也对疾病进程有着重要影响。课题组前期研究证实，髓鞘淋巴相关蛋白（MAL）是一种抑制口腔鳞癌发展的重要分子，成功诱导MAL基因敲除小鼠口腔鳞癌模型后，发现MAL缺失增加小鼠对口腔鳞癌的易感性，并促进肿瘤发展；同时还发现，MAL缺失小鼠骨髓诱导的巨噬细胞向M2型极化，mTOR与转录因子STAT6的磷酸化水平明显升高。由此提出科学假说，MAL通过mTOR-STAT6调控肿瘤微环境中巨噬细胞向M2型极化，影响口腔鳞癌的发生发展。本研究将利用流式细胞术分析MAL缺失后，口腔鳞癌微环境中巨噬细胞表型的变化，并通过完全骨髓嵌合体和基因双敲除小鼠阐明调控机制，为临床诊断和治疗口腔鳞癌新技术的发展提供实验依据。

Oral squamous cell carcinoma (OSCC) is a severe threat to human health. The development of OSCC is not only depending on tumor cells, but also closely related to the aberrant functions of immune cells, especially for macrophages and the changes of their complex intracellular signal transductions in tumor microenvironment. Our previous researches showed that MAL (myelin and lymphocyte-associated protein) was an important candidate tumor suppressor gene in OSCC. The preliminary experimental results showed that MAL knockout mice were more susceptible to oral squamous cell carcinoma than control groups and MAL deficiency promoted the developmend and progression of tumor. It was also found that MAL knockout induced macrophages to M2 polarization and increased the phosphorylation of mTOR and STAT6 in bone marrow derived macrophages. Therefore, we supposed that MAL promoted macrophages to M2 polarization through mTOR-STAT6 axis in OSCC. This study would use flow cytometry to analyze the phenotypic changes in MAL deficiency macrophages during OSCC. Then we clarified the regulatory mechanisms by full chimeras and double knockout mice. In summary, the research could provide an experimental basis for clinical treatment and diagnosis new strategies of OSCC.