肿瘤浸润T淋巴细胞（Tumor infiltrating T lymphocytes，TIL）的抗肿瘤能力与其线粒体的代谢状态密切相关。去乙酰化酶Sirt3是调控线粒体代谢状态的关键分子，本实验室最新的研究发现Sirt3的去SUMO化修饰可增强其活性。同时，本项目前期的工作表明，在肿瘤浸润T淋巴细胞的耗竭过程中Sirt3的活性下降，而Sirt3的去SUMO化修饰则可增强CD8+T细胞的线粒体代谢与存活能力。因此，我们推测Sirt3及其去SUMO化修饰可能通过调控线粒体内的乙酰化修饰与代谢功能，影响肿瘤浸润T淋巴细胞的抗肿瘤能力。本项目将重点研究以下问题：1.明确肿瘤浸润T淋巴细胞耗竭过程中的Sirt3及其SUMO化修饰的变化；2.明确Sirt3及其去SUMO化修饰对肿瘤浸润T淋巴细胞抗肿瘤免疫的影响；3.明确Sirt3及其去SUMO化修饰调控肿瘤浸润T淋巴细胞线粒体代谢的作用及分子机制。

The anti-tumor ability of tumor infiltrating T lymphocytes (TIL) is closely related to its mitochondrial metabolic status. Deacetylase Sirt3 is a key molecule that regulates the activities of various metabolic pathway in mitochondria. Our recent studies have found that the de-SUMOylation of Sirt3 can enhance its deacetylase activity and increase mitochondrial metabolism. The preliminary work of this project suggested that the activity of Sirt3 decreased during the exhaustion of tumor infiltrating T lymphocytes, and the de-SUMOylation of Sirt3 can enhance the mitochondrial metabolism and survival of CD8+ T cells. Therefore, this project speculates that Sirt3 and its de-SUMOylation may affect the anti-tumor ability of tumor infiltrating T lymphocytes by regulating acetylation modification and metabolism in mitochondria. This project will focus on the following issues: 1. To clarify the change of Sirt3 and its SUMOylation during the exhaustion of tumor-infiltrating T lymphocytes; 2. To clarify the effect of Sirt3 and its de-SUMOylation on the anti-tumor immunity of tumor-infiltrating T lymphocytes; 3. To clarify the role and molecular mechanism of Sirt3 and its de-SUMOylation to regulate the mitochondrial metabolism of tumor infiltrating T lymphocytes.