近年来，Vγ9Vδ2 T细胞在肿瘤免疫治疗领域备受关注，同时热疗作为肿瘤治疗的新型疗法已广泛应用于临床。文献报道热应激可通过增强免疫细胞功能而杀伤肿瘤，但是对Vγ9Vδ2 T细胞的功能影响尚不清楚。因此，我们模拟体内热作用探讨热应激对Vγ9Vδ2 T细胞的功能影响及机制。前期的工作发现在40℃培养温度下既不影响Vγ9Vδ2 T细胞活力又能够模拟热应激反应；并且热应激后c-Jun表达显著上调，作为MAPK信号通路的核转录因子可影响细胞增殖分化及炎症因子的分泌。本项目拟解决的关键科学问题：（1）热应激对Vγ9Vδ2 T细胞增殖分化和肿瘤杀伤功能产生如何的影响；（2）热应激通过MAPK信号通路调控Vγ9Vδ2 T细胞抗肿瘤功能的具体作用机制是什么。总之，本项目将揭示热应激调控Vγ9Vδ2 T细胞抗肿瘤功能的作用及机制，为下一步通过热应激调控Vγ9Vδ2 T细胞临床抗肿瘤应用提供科学依据。

In recent years, Vγ9Vδ2 T cells have attracted attention in the field of tumor immunotherapy. And hyperthermia has been widely used as a new treatment for tumor therapy. It is reported that thermal stress may achieve the purpose of killing tumor cells by enhancing immune cell function, but the thermal effects on the function of Vγ9Vδ2 T cells is unclear. Therefore, we explored the effects and mechanisms of thermal stress on Vγ9Vδ2 T cells in vitro by simulating thermal effects in vivo. Our previous work found that it does not affect the vitality of Vγ9Vδ2 T cells and can simulate the thermal stress response at 40℃ culture; and the expression of c-Jun gene was significantly up-regulated which can affect cell proliferation and inflammatory cytokines secretion involvement as a nuclear transcription factor in the MAPK signaling pathway. We will address our scientific questions with the following specific aims: (1) How does thermal stress affect Vγ9Vδ2 T cell proliferation and tumor killing function; (2) What’s the mechanism of thermal stress regulates the anti-tumor function of Vγ9Vδ2 T cell through MAPK signal pathway. In conclusion, this project will reveal the mechanism of thermal stress regulating the anti-tumor function of Vγ9Vδ2 T cells, and provide scientific basis for the antitumor clinical application of Vγ9Vδ2 T cell by the thermal regulation.