非小细胞肺癌中医辨证分型与肿瘤免疫微环境的关系  

Relationship Between Traditional Chinese Medicine Syndrome Differentiation and Tumor Immune Microenvironment in Non-small Cell Lung Cancer

作　　者：肖真真 朱燕娟[1,2,3] 刘译鸿 常雪松[1] 陈亚栋 余娅娅 何怡瀚 张海波[1,2,3,4] XIAO Zhen-zhen;ZHU Yan-juan;LIU Yi-hong;CHANG Xue-song;CHEN Ya-dong;YU Ya-ya;HE Yi-han;ZHANG Hai-bo(Guangdong Provincial Hospital of Traditional Chinese Medicine,the Second Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510120 Guangdong,China;Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome,Guangzhou 510120 Guangdong,China;Guangdong-Hong Kong-Macao Joint Lab on Chinese Medicine and Immune Disease Research,Guangzhou 510120 Guangdong,China;State Key Laboratory of Dampness Syndrome of Chinese Medicine,the Second Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510120 Guangdong,China)

机构地区：[1]广东省中医院(广州中医药大学第二附属医院),广东广州510120 [2]广东省中医证候临床研究重点实验室,广东广州510120 [3]粤港澳中医药与免疫疾病研究联合实验室,广东广州510120 [4]广州中医药大学第二附属医院省部共建中医湿证国家重点实验室,广东广州510120

出　　处：《中医肿瘤学杂志》2022年第4期14-20,共7页Journal of Oncology in Chinese Medicine

基　　金：广东省中医院中医药科学技术研究专项(编号:YN2018ZD05);2020广东省科技创新战略专项资金(粤港澳联合实验室)项目(编号:2020B1212030006)。

摘　　要：目的基于Opal多重染色技术探讨非小细胞肺癌肿瘤微环境与中医寒热证、气虚证、痰湿证、阴虚证、热毒证、血瘀证的关系。方法收集ⅢB期及以上非小细胞肺癌(non-small cell lung cancer,NSCLC)初治患者的肿瘤组织样本,采用多重免疫荧光染色法检测肿瘤免疫微环境中10个指标(CD3、CD4、CD8、CD68、CD163、FOXP3、LAG3、TIM3、PD-1、PD-L1)的蛋白表达情况,分析其与临床特征及中医证型的关系。结果本研究共纳入69例患者,其中61例患者记录了中医寒热证型,56例患者记录了中医气虚证、痰湿证、阴虚证、热毒证、血瘀证证型,其中伴有气虚证、痰湿证的患者居多。分析临床特征与中医辨证分型、肿瘤免疫微环境的关系发现,Ⅳ期患者中,CD8+T细胞表达的比例最高;男性患者中痰湿证的比例比女性高,PD-L1的表达比例最高;非L858R敏感突变患者中痰湿证居多,EGFR突变中TIM3表达比例最高(P<0.05)。中医辨证分型与肿瘤免疫微环境的分析结果提示,热证患者中CD4+T细胞及CD8+T细胞表达水平更高,阴虚证与肿瘤区域中CD8+T细胞的表达负相关,痰湿证与整个区域中PD-L1的表达呈负相关(P<0.05)。结论中医热证患者的肿瘤微环境更偏向于免疫“热肿瘤”,中医寒证向热证转化可能提高患者对免疫疗法的应答率,中医痰湿证患者的肿瘤微环境可能处于免疫抑制状态。Objective To explore the relationship between the tumor microenvironment of non-small cell lung cancer(NSCLC)with traditional Chinese medicine(TCM)syndromes of cold-heat syndrome,qi deficiency syndrome,phlegm-dampness syndrome,yin deficiency syndrome,heat toxin syndrome and blood stasis syndrome based on Opal multiple staining technique.Methods Tumor tissue samples from newly-treated patients with NSCLC at stageⅢB or above were collected,the protein expression of 10 indicators(CD3,CD4,CD8,CD68,CD163,FOXP3,LAG3,TIM3,PD-1,and PD-L1)in the tumor immune microenvironment was detected by multiplex immunofluorescence staining,and their relationships with clinical features and TCM syndromes were analyzed.Results A total of 69 NSCLC patients were included in the study,of which 61 patients were differentiated as cold-heat syndrome,and 56 patients were differentiated as qi deficiency syndrome,phlegm-dampness syndrome,yin deficiency syndrome,heat toxin syndrome and blood stasis syndrome respectively.Among them,most of the patients were complicated with qi deficiency syndrome and phlegm dampness syndrome.The analysis of the relationship of clinical characteristics with TCM syndrome types and tumor immune microenvironment indicators showed that the proportion of CD8+T cell expression in stageⅣpatients was the highest,higher proportion of phlegm-damp syndrome and higher expression level of PD-L1 were found in the male patients,patients with non-L858R sensitive mutation were mostly differentiated as phlegm-dampness syndrome and patients with EGFR mutations had higher TIM3 expression(P<0.05).The relationship of TCM syndrome types with tumor immune microenvironment indicators showed that patients with heat syndrome had higher expression levels of CD4+T cells and CD8+T cells,yin deficiency syndrome was negatively correlated with the expression of CD8+T cells around the tumor tissue,and phlegm-dampness syndrome was negatively correlated with the expression of PD-L1 in the whole region(P<0.05).Conclusion The tumor microenvironmen

关 键 词：非小细胞肺癌 中医辨证分型 肿瘤免疫微环境 

分 类 号：R734.1[医药卫生—肿瘤] R273[医药卫生—临床医学]