病证结合的中医药维持治疗方案干预晚期非小细胞肺癌免疫逃逸的临床研究  

Clinical study on the intervention of advanced NSCLC immuneescape with traditional Chinese medicine maintenance therapy of combination of diseases and syndrome

作　　者：张朋[1] 刘苓霜[1] 姜怡[1] 沈丽萍[1] 姜维洁[1] ZHANG Peng;LIU Ling-shuang;JIANG Yi;SHEN Li-ping;JIANG Wei-jie(Six Department of Cancer,Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China)

机构地区：[1]上海中医药大学附属龙华医院肿瘤六科,上海200032

出　　处：《中华中医药杂志》2018年第11期5234-5239,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然青年科学基金项目(No.81703987);上海市科学技术委员会项目(No.16401970800);龙医学者(育苗计划)(No.LYTD-43)~~

摘　　要：目的:观察中医病证结合治疗方案在晚期非小细胞肺癌(NSCLC)维持治疗中的疗效,并从免疫逃逸角度阐明其机制。方法:采用前瞻性、自身前后对照设计,将65例一线治疗后疾病控制(完全缓解/部分缓解/疾病稳定)的晚期NSCLC患者进行中医病证结合维持治疗。观察该方案对晚期NSCLC患者疾病进展时间(TTP)的影响,同时检测50名正常人及65例患者治疗前后免疫指标,包括可溶性程序性死亡分子1配体(sPD-L1)、CD4^+CD25^+CD127-调节性T细胞(CD4^+CD25^+CD127-Tregs)的变化,从免疫逃逸角度探索疗效机制。结果:中医病证结合维持治疗晚期NSCLC患者中位TTP 96.0d;晚期NSCLC患者外周血sPD-L1浓度、CD4^+CD25^+CD127-Tregs百分比高于正常人[(0.193±0.068)ng/mL vs (0.119±0.045)ng/mL,P=0.001]、[(3.90±1.21)%vs (2.68±0.88)%,P=0.001];中医维持治疗后sPD-L1、CD4^+CD25^+CD127-Tregs水平均成下降趋势;中医维持治疗后TTP延长组(36例)sPD-L1有效率(下降+稳定)高于未延长组(29例),差异无统计学意义(86.1%vs 75.9%,P=0.424),CD4^+CD25^+CD127-Tregs有效率(下降+稳定)高于未延长组,差异有统计学意义(86.1%vs 68.9%,P=0.034)。结论:中医病证结合维持治疗可以延长晚期NSCLC患者一线治疗后疾病进展时间;其机制可能是通过下调sPD-L1、CD4^+CD25^+CD127-Tregs水平来实现。Objective： To observe the efficacy of traditional Chinese medicine（TCM） with the combination of diseases and syndrome treatment in the maintenance treatment of advanced non-small cell lung cancer（NSCLC） and elucidate the mechanism from the perspective of immune escape. Methods： The prospective and self-controlled before-after contrast design was used, and the 65 patients of advanced NSCLC whose disease were controlled after first-line treatment（complete remission/partial remission/disease stabilization） were accepted the maintenance treatment of TCM with combination of diseases and syndrome. The effect of time to progress（TTP） of advanced NSCLC patients were observed by TCM with the combination of diseases and syndrome theatment, at the same time, the immune indexes of 50 normal people and 65 patients were measured beforeafter treatment, including soluble progress-ligand^（-1）（sPD-L1） and CD4^＋CD25^＋CD127-regulatory T cells（CD4^＋CD25^＋CD127-Tregs）, and explored the efficacy mechanism from immuneescape. Results： The TTP of advanced NSCLC patients after the maintenance treatment of TCM was 96 days; The levels of sPD-L1 and CD4^＋CD25^＋CD127-Tregs in peripheral blood of advanced NSCLC patients were higher than the normal people [（0.193±0.068）ng/mL vs（0.119±0.045）ng/mL, P=0.001], [（3.90±1.21）% vs（2.68±0.88）%, P=0.001]. After maintenance treatment of TCM, both sPD-L1 and CD4^＋CD25^＋CD127-Tregs decreased, the sPD-L1 effective rate（decrease ＋ stability） of the TTP prolongation group was higher than the non-prolongation group, and existed significantly difference（86.1% vs 75.8%, P=0.424）, the CD4^＋CD25^＋CD127-Tregs effective rate（decrease ＋ stability） of the TTP prolongation group was higher than the non-prolongation group, and existed significantly difference（86.1% vs 68.9%, P=0.034）. Conclusion： TCM maintenance therapy can prolong the time of disease progression in advanced NSCLC patients after first-line treatment, and the me

关 键 词：非小细胞肺癌 中医药 免疫逃逸 维持治疗 病证结合 

分 类 号：R273[医药卫生—中西医结合]