口腔鳞癌细胞中缺氧-CD73介导的腺苷信号促进单核细胞向M-MDSCs转化的机制研究

Hypoxia-adenosinergic pathway facilitates tumor immune escape. Based on our previous study, we demonstrate that CD73-generated adenosine from hypoxic oral squamous cell carcinoma (OSCC) cancer cells promotes the transform process of monocytes to immunosuppressive monocytic myeloid-derived suppressor cells (M-MDSCs). This project is anticipated to discover the underlying molecular mechanism during this process. Firstly，we plan to investigate the function of CD73-generated adenosine during the transform of monocytes to M-MDSCs. Secondly, the underlying molecular mechanism of this process will be illustrated. Thirdly, the effects of in vivo CD73 blockade on this transform process will be estimated. Finally, the relationship among hypoxia-adenosinergic pathway and the surface makers of M-MDSCs will be discussed via human OSCC tissue microarrays. This project will contribute to a better understanding of the mechanism in hypoxia-adenosinergic-induced immune escape, providing the rationale of immunotherapy targeting CD73 in OSCC.

腺苷信号通路是缺氧介导肿瘤免疫逃逸的重要机制之一。本项目结合申请人前期研究基础，围绕“口腔鳞癌细胞中缺氧-CD73介导的腺苷信号如何促进单核细胞向单核样髓源性抑制细胞（M-MDSCs）转化”这一科学问题，拟从以下四个方面展开研究：①口腔鳞癌细胞中缺氧-CD73介导的腺苷信号促进单核细胞获得M-MDSCs表型及免疫抑制功能的研究；②口腔鳞癌细胞中缺氧-CD73介导的腺苷信号促进单核细胞向M-MDSCs转化的分子机制研究；③体内实验研究阻断CD73对单核细胞向M-MDSCs转化的影响；④人类口腔鳞癌组织中缺氧-腺苷通路与M-MDSCs的相关性研究。本项目旨在揭示口腔鳞癌细胞中缺氧-CD73介导的腺苷信号促进单核细胞向M-MDSCs转化的具体机制，进一步阐明缺氧-腺苷通路在口腔鳞癌免疫逃逸中的作用，探索CD73作为口腔鳞癌免疫治疗靶点的可行性。

腺苷信号通路是缺氧介导肿瘤免疫逃逸的重要机制之一。本项目结合申请人前期研究基础，围绕“口腔鳞癌细胞中缺氧-CD73介导的腺苷信号如何促进单核细胞向单核样髓源性抑制细胞（M-MDSCs）转化”这一科学问题，完成了以下研究：1. 口腔鳞癌细胞中缺氧-CD73介导的腺苷信号促进单核细胞获得M-MDSCs表型及免疫抑制功能的研究；2. 体内实验研究阻断CD73对单核细胞向M-MDSCs转化的影响；3. 人类口腔鳞癌组织中缺氧-腺苷通路与M-MDSCs的相关性研究。4. 其他免疫治疗靶点在口腔鳞癌中的表达及分子机制