T细胞的糖代谢在结直肠癌发生中的作用机制

T细胞在维持肠道免疫稳态中发挥重要的作用，其功能紊乱是导致结直肠癌发生的重要因素。糖代谢为T细胞的存活和功能发挥提供能量和碳源，而糖代谢在T细胞维持肠道免疫稳态和控制结直肠癌发生中的作用机制亟待研究。申请人前期工作阐明了特定糖代谢特征在Treg细胞维持免疫稳态中的作用机制，揭示了糖代谢途径促进CD8+T细胞免疫应答的分子机理。鉴于此，推测T细胞的糖代谢在肠道免疫稳态和结直肠癌发生中起重要作用。本项目将鉴定控制T细胞糖代谢的关键酶3-5种，应用单细胞转录组学、蛋白质组学、代谢组学、转基因小鼠和肿瘤模型等技术，解析关键酶介导的糖代谢途径在T细胞维持肠道免疫稳态和抑制结直肠癌发生中的作用机制，探索干预糖代谢特征治疗结直肠癌的策略。本项目将为结直肠癌治疗提供新的靶点，为干预结直肠癌发生提供新的策略。

T cells are essential for maintaining gut immune homeostasis and T cell dysfunction can trigger colorectal carcinogenesis. T cells require glucose metabolism to obtain carbon and energy for survival and function. However, how glucose metabolism participates in T cell-mediated gut immune homeostasis and colorectal cancer prevention remains largely unknown. Our previous studies reveal that specific glucose metabolic programs are required for regulatory T cell-mediated immune homeostasis, and clarify the molecular mechanism by which glucose metabolism regulates CD8+ T cell immune responses. Therefore, we hypothesize that glucose metabolism of T cells plays an important role in gut immune homeostasis and colorectal carcinogenesis. In the proposed project, we will identify 3-5 crucial enzymes controlling specific glucose metabolic programs of T cells, and investigate the function and mechanism of T cell glucose metabolism in the regulation of gut immune homeostasis and colorectal carcinogenesis, using single cell transcriptomics, proteomics, metabolomics, transgenic mice and tumor models. We will also explore the potential applications in colorectal cancer treatment by targeting specific glucose metabolic programs. These studies will hold promise for providing new therapeutic targets and strategies for colorectal cancer treatment.