从“三焦-营卫”气化失常角度探析肿瘤T细胞耗竭机制

Mechanism of Tumor T Cell Exhaustion from Perspective of"Sanjiao-Yingwei"Qi Transformation Malfunction

为推动三焦理论、营卫理论的创新转化应用,该文试将“三焦-营卫”气化理论应用于肿瘤病论治之中,将其与T细胞耗竭机制相融合以阐述其科学内涵,并运用网络药理学与生物信息学阐发调畅“三焦-营卫”气化方抗肿瘤机制与T细胞耗竭相关性。“三焦-营卫”气化功能与人身免疫代谢功能密切,“三焦-营卫”气化体系构成了细胞内外环境免疫代谢交流体系。癌毒由伏郁三焦的秽浊杂气所生,癌毒长期伏郁三焦所致的是导致T细胞耗竭的首要因素,其与肿瘤微环境中存在的高肿瘤抗原负荷长期激活T细胞受体相关。三焦气化不利生痰聚瘀是促使T细胞耗竭的主要因素,其与免疫抑制肿瘤微环境中营养剥夺、脂质堆积、高乳酸水平相关,亦与肿瘤微环境中肿瘤相关成纤维细胞及血小板释放转化生长因子-β、上调表达程序性死亡受体-1表达相关。三焦气化不利所致的营卫损伤,与耗竭T细胞效应功能累进式丧失、细胞能量代谢紊乱等异常表现相类似。桂枝汤、升明汤、温胆汤等调畅“三焦-营卫”气化方可通过多靶点多通路以纠正T细胞耗竭发挥抗肿瘤作用,缺氧诱导因子-1α(HIF-1α)可能是上述三方纠正T细胞耗竭主要通路之一。通过生物信息学手段发现HIF-1α可能是常见肿瘤中重要预后指标之一,运用调畅“三焦-营卫”气化法在临床实践中可能对改善肿瘤患者预后具有重要作用。

In order to promote the innovative application of Sanjiao theory and Yingwei theory,this paper tries to apply the"Sanjiao-Yingwei"Qi transformation theory to the treatment of tumor diseases,integrating it with T cell exhaustion mechanism to elaborate on its scientific connotation and using network pharmacology and bioinformatics to elucidate the correlation between the anti-tumor mechanism of"Sanjiao-Yingwei"Qi transformation and T cell exhaustion.The"Sanjiao-Yingwei"Qi transformation function is closely related to the immunometabolic ability of the human body,and the"Sanjiao-Yingwei"Qi transformation system constitutes the immunometabolic exchange system within and outside the cellular environment.Cancer toxicity is generated by the fuzzy Sanjiao Qi,and the long-term fuzzy Sanjiao Qi is the primary factor leading to T cell exhaustion,which is related to the long-term activation of T cell receptors by the high tumor antigen load in the tumor microenvironment.Qi transformation malfunction of the Sanjiao produces phlegm and collects stasis,which contributes to T cell exhaustion and is correlated with nutrient deprivation,lipid accumulation,and high lactate levels in the immunosuppressed tumor microenvironment,as well as with the release of transforming growth factor-βand upregulated expression of programmed death receptor-1 by tumor-associated fibroblasts and platelets in the tumor microenvironment.Ying and Wei damage due to Sanjiao Qi transformation malfunction is similar to the abnormal manifestations such as progressive loss of exhausted T cell effector function and disturbance of cellular energy metabolism.Guizhi decoction,Shengming decoction,and Wendan decoction can correct T cell exhaustion and exert anti-tumor effects through multi-target and multi-pathways by regulating"Sanjiao-Yingwei"Qi transformation,and hypoxia inducible factor-1α(HIF-1α)may be one of the main pathways to correct T cell exhaustion.It was found that HIF-1αmay be one of the important prognostic indicators in common tumors by bioinformatics.The use of the"Sanjiao-Yingwei"Qi transformation method may play an important part in improving the prognosis of tumor patients in clinical practice.