肿瘤代谢微环境糖酵解产物与免疫体系的相互作用存在于肿瘤演进全程，其核心是肿瘤糖酵解产物通过对T细胞表型及功能的调控，启动免疫抑制体系，最终导致各种肿瘤免疫治疗方法疗效不好。现行研究缺乏合适的可视化分子网络研究技术，未获得肿瘤代谢微环境产物与T细胞相互作用的动态变化数据，不清楚代谢微环境导致T细胞对肿瘤产生免疫耐受的调控机制。本项目利用免疫缺陷小鼠建立肿瘤不同演进阶段的代谢微环境和人T细胞系统的共存平台；形成肿瘤代谢标志物和T细胞表型/功能进行精准比对的研究平台。利用靶向代谢微环境标志物的micro-PET和光声成像对肿瘤代谢微环境特征进行定性、定量检定，利用可活体显示Teff和Treg表型/功能特征的生物标志物逻辑门成像技术，探索肿瘤演进过程中代谢微环境关键分子与Teff/Treg生物标志物变化的逻辑关系，阐明肿瘤代谢微环境对T细胞表型及功能的调控机制，明确其关键调控环节和关键调控分子。

The interaction between glycolytic products and immune system of tumor metabolic microenvironment exists in the whole process of tumor progress. Its core is to activate the immune suppression system through the regulation of T cell phenotype and function, and eventually lead to the immune tolerance of T cell system to tumor antigen. Current studies lack of appropriate visualized molecular network research technology, and the dynamic change data of the interaction between tumor metabolic microenvironment products and T cells are not obtained. Also, the regulatory mechanism of T cells' immune tolerance to tumor induced by metabolic microenvironment was not studied. In this study, immune-deficient NCG mice were used to establish the metabolic microenvironment and human t-cell system in different stages of tumor progress, and to form a research platform for accurate comparison of tumor metabolic microenvironment biomarkers and T cell phenotypes and functions. Micro-pet and photoacoustic imaging of targeted metabolic microenvironment markers were used for accurate qualitative and quantitative verification of tumor metabolic microenvironment characteristics, and logic-gate biomarker imaging technology that can accurately reflect Teff and Treg phenotypes and functional characteristics was used. This study aim to explore the logical relationship between the key molecules of metabolic microenvironment and the changes of Teff/Treg biomarkers in the process of tumor development, to clarify the regulatory mechanism of tumor metabolic microenvironment on the phenotype and function of T cells, and to clarify its key regulatory links and key regulatory molecules.