胶质瘤是最常见的颅内恶性肿瘤，近年来免疫疗法已彰显发展潜力和应用前景。我们前期研究发现，癌-睾丸抗原OY-TES-1（OY）在除睾丸外的正常组织几乎不表达，在胶质瘤高表达，其表达越高患者预后越差，与其逃避免疫监控有关。初步研究显示，OY与PD-L1具有共同的靶标miR-326。已知PD-L1是重要的免疫检查点，OY可能作为竞争性内源RNA（CeRNA）吸附miR-326，调控PD-L1参与免疫逃逸，其分子机制值得深究。为证明OY是PD-L1的CeRNA，本课题拟先进行关系验证：⑴OY与PD-L1共表达；⑵OY对PD-L1的调控具有miRNA依赖性；⑶OY能影响PD-L1的转录水平和蛋白水平。其次，进行功能验证：构建双荧光示踪的小鼠原位移植瘤模型，从肿瘤细胞、微环境、免疫细胞等多方面观察OY/miR-326协同调控PD-L1产生的影响，为肿瘤免疫治疗和靶向药物的选择提供新思路。

Glioma is the most common intracranial malignancy. Immunotherapy has demonstrated its development potential and application prospects in recent years. Our previous study found that cancer-testis antigen OY-TES-1 is not expressed in normal tissues except for testis, and is highly expressed in gliomas. The higher its expression, the worse the prognosis of patients and it may be related to immune tolerance. Preliminary studies have shown that OY-TES-1 and PD-L1 have a common target miR-326. It is known that PD-L1 is an important immune checkpoint. Whether OY-TES-1 acts as a competitive endogenous RNA (CeRNA) to adsorb miR-326, and thus the molecular mechanism regulating PD-L1's involvement in tumor immune escape is worth further studying. In order to prove that OY-TES-1 is the CeRNA of PD-L1, this subject should verify the relationship: (1) Co-expression of OY-TES-1 and PD-L1; (2) OY-TES-1 has miRNA-dependent regulation of PD-L1; (3) OY-TES-1 can affect PD-L1 in the transcriptional and protein levels. Subsequently, functional verification was also performed. An orthotopic xenograft mouse model with dual-fluorescent traces was constructed, then the effects of OY-TES-1/miR-326 coordinated regulation of PD-L1 from tumor cells, tumor microenvironment, and immune cells was observed. This study will help to provide new ideas for tumor immunotherapy and targeted drug selection.