丙酮酸脱氢酶复合物是参与葡萄糖氧化的关键酶。它受丙酮酸脱氢酶激酶和丙酮酸脱氢酶磷酸酶调节。研究表明，丙酮酸脱氢酶激酶 1 (PDHK1) 是葡萄糖代谢中的关键酶，其行为类似于癌基因。它在肿瘤中高表达，与患者预后不良相关。然而，关于 PDHK1 如何影响免疫细胞功能的研究有限。我们建立了自然杀伤 (NK) 细胞耗竭模型，以研究二氯乙酸 (DCA) 对 NK 细胞功能的影响。通过流式细胞术探索 NK 细胞产生颗粒酶 B、IFN-γ、TNF-α 和 CD107a。实时活细胞成像系统用于监测NK细胞对抗肿瘤细胞的能力。利用Seahorse分析仪测量NK细胞的耗氧率（OCR）和细胞外酸化率（ECAR）。该小鼠模型用于研究 DCA 与辅助 NK 细胞输注相结合的潜力。我们的研究表明，肝细胞癌 (HCC) 微环境介导 NK 细胞耗竭、PDHK1 高表达和细胞因子分泌减少。我们发现 PDHK1 抑制剂 DCA 增强了浸润肿瘤微环境的耗尽的 NK 细胞的活性和功能。此外，在皮下 HCC 小鼠模型中，DCA 与 NK 细胞治疗相结合可延缓癌症进展。这项研究表明 DCA 在挽救 NK 细胞耗竭和引发抗肿瘤免疫方面的潜力。

Pyruvate dehydrogenase complex is a crucial enzyme involved in the oxidation of glucose. It is regulated by pyruvate dehydrogenase kinase and pyruvate dehydrogenase phosphatase. Studies have demonstrated that pyruvate dehydrogenase kinase 1 (PDHK1), a key enzyme in glucose metabolism, behaves like oncogenes. It is highly expressed in tumors and is associated with poor patient prognosis. However, there is limited research on how PDHK1 affects immune cell function. We have established a model of natural killer (NK) cell exhaustion to investigate the impact of dichloroacetate (DCA) on NK cell function. The production of Granzyme B, IFN-γ, TNF-α, and CD107a by NK cells was explored by flow cytometry. The real-time live cell imaging system was used to monitor the ability of NK cells against tumor cells. The Seahorse analyzer was utilized to measure the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) of NK cells. The mouse model was used to investigate the potential of combining DCA with adjuvant NK cell infusion. Our study demonstrated that the hepatocellular carcinoma (HCC) microenvironment mediated NK cellular exhaustion, high expression of PDHK1 and reduced cytokine secretion. We discovered that the PDHK1 inhibitor DCA enhances the activity and function of exhausted NK cells infiltrating the tumor microenvironment. Furthermore, in a subcutaneous HCC mouse model, DCA combined with NK cell treatment resulted in retarding cancer progression. This study indicates the potential of DCA in rescuing NK cell exhaustion and eliciting anti-tumor immunity.