从“免疫编辑”角度探讨恶性肿瘤的五期演变生物学基础

Biological Basis of Five-phase Evolution of Malignant Tumors from Perspective of"Immune Editing"

免疫逃逸是肿瘤的十大特征之一,在肿瘤的发生发展中发挥着至关重要的作用。免疫编辑指肿瘤细胞通过免疫清除-免疫平衡-免疫逃逸的模式,对机体免疫系统进行重塑与编辑,将肿瘤微环境中的免疫细胞“改造”成免疫抑制细胞,实现免疫逃逸。五期演变是李杰教授对肿瘤病机发展的总结,认为肿瘤的渐次发展遵循“虚-寒-毒-闭-衰”的核心病机,其中“郁”贯穿始终,癌毒是核心。该文以免疫编辑为切入点,将肿瘤细胞的表型特征与李杰老师的五期演变核心病机相结合,揭示恶性肿瘤五期演变的生物学基础,分析从虚到寒阶段的突出变化是机体免疫监视功能下降,从毒到闭阶段的突出变化是免疫逃逸,而五期演变的最终阶段——衰,是机体免疫衰竭的最终结局,郁是肿瘤免疫编辑的助推剂。以此提出扶正解毒法调控免疫编辑截断肿瘤的五期演变,益气温阳扶正气,恢复机体免疫监视功能;解毒宣闭转毒势,逆转免疫逃逸;以和为法,维持免疫细胞/免疫抑制细胞的动态平衡;解郁之法,截断肿瘤免疫编辑,为中医药的微观辨证施治提供一定的借鉴。在未来的研究中,还需要对益气温阳法、解毒宣闭法、两者联合及解郁法对免疫编辑调控的具体机制进一步地探索,寻找出特异性的中药及作用靶点,为中医药调控肿瘤免疫编辑提供更加充分的证据。

Immune escape is one of the ten hallmarks of tumors,which plays an important role in the occurrence and development of tumors.Immune escape refers to a process where tumor cells remodel and edit the immune system through the model of immune clearance,immune balance,and immune escape to"transform"the immune cells into immunosuppressive cells in the tumor microenvironment,so as to support immune escape.The five-stage evolution is the summary of tumor pathogenesis by professor LI Jie.He believes that the gradual development of tumors follows the core pathogenesis of"deficiency-cold-toxin-obstructioncollapse",in which"depression"runs through the whole process,and cancer toxin is the key.Based on immune editing,this paper combined phenotypic characteristics of tumor cells with the core pathogenesis of the five-stage evolution of professor LI to reveal the biological basis of malignant tumor five-stage evolution.The results indicate that the prominent change from deficiency to cold is the reduction of immune surveillance and the prominent change from toxin to obstruction is immune escape.The final stage of collapse is the outcome of immune failure.Depression is the booster of tumor immune editing.Therefore,the method of reinforcing the healthy Qi and removing toxins was proposed to regulate the immune editing and cut off the five-stage evolution of tumors.Supplementing Qi and warming Yang can reinforce the healthy Qi and restore immune surveillance.Removing toxins and dredging can reverse toxins and immune escape.The harmonizing method can maintain the dynamic balance of immune cells/immunosuppressive cells.Resolving depression can truncate tumor immune editing.Those methods can provide a certain reference for the treatment based on microscopic syndrome differentiation in traditional Chinese medicine(TCM).In future studies,it is necessary to further explore the specific mechanism of the regulation of immune editing with the methods of supplementing Qi and warming Yang,removing toxins and dredging,their combination,and resolving depression,so as to find out specific Chinese medicines and targets and provide more sufficient evidence for the regulation of tumor immune editing by TCM.