肿瘤细胞和活化T细胞因相似的代谢重编程存在代谢竞争，影响抗肿瘤免疫应答。肿瘤微环境富含去甲肾上腺素（NE），可激活肾上腺素β受体（βAR）信号通路削弱肿瘤免疫治疗疗效，但机制不明。我们最近发现，NE可上调肿瘤细胞HIF-1α、GLUT-1、LDHA和PDK1等糖酵解相关基因的表达，促进肿瘤细胞的糖酵解，但NE全面抑制了活化CD8+ T细胞的葡萄糖、脂肪酸和氨基酸代谢。因此，我们推测βAR信号通路可能加剧肿瘤细胞与T细胞的代谢竞争，削弱免疫治疗的疗效。本项目将模拟肿瘤微环境中βAR的过度激活状态，研究βAR信号通路双向调控肿瘤细胞和T细胞代谢重编程的可能机制：激活βAR/cAMP/PKA/CREB信号通路促进肿瘤细胞代谢重编程，激活βAR/cAMP/ICER和βAR/β-arrestin 2/NFκB信号通路抑制T细胞代谢重编程。据我们所知，目前国内外尚未见从这一角度研究代谢竞争的类似报道。

Metabolic competition exists between tumor cells and activated T cells because of similar metabolic reprogramming, which influences antitumor immune response. Norepinephrine (NE) enriched in the tumor microenvironment, can activate β-adrenergic receptor (βAR) to weaken the efficacy of immunotherapy. However, its mechanisms have yet to be elucidated. We recently found that NE could promote the glycolysis of tumor cells through up-regulating the expression of glycolysis related genes, such as HIF-1α, GLUT-1, LDHA and PDK1. Conversely, NE inhibited the metabolism of glucose, fatty acid and amino acids in activated CD8+ T cells. Therefore, we speculate that the βAR signaling pathway could exacerbate metabolic competition between tumor cells and T cells to weaken the efficacy of immunotherapy. In this project, we plan to mimic the status of high levels of NE in the tumor microenvironment, to explore the effects and the underlying mechanisms of βAR signaling pathway on metabolic reprogramming: activating βAR/cAMP/PKA/CREB signaling pathway to promote metabolic reprogramming of cancer cells, but activating βAR/cAMP/ICER and βAR/β-arrestin 2/NFκB signaling pathways to inhibit metabolic reprogramming of T cells. So far as we know, there is no literature reported regarding metabolic competition from this perspective.