晚期NSCLC组织巨噬细胞表面Tim-3表达与临床特征和预后的关系  

Correlation between Tim-3 on the surface of TAM and pathological features and prognosis in advanced NSCLC patients

作　　者：籍强[1] 吕骏卿 赵鑫[3] 荣伟强 JI Qiang;LYU Junqing;ZHAO Xin;RONG Weiqiang(Department of Thoracic Cardiovascular Surgery,the First Affiliated Hospital of Hebei North University,Zhangjiakou,Hebei 075000,China;Department of Emergency,the First Affiliated Hospital of Hebei North University,Zhangjiakou,Hebei 075000,China;Department of Radiotherapy,the First Affiliated Hospital of Hebei North University,Zhangjiakou,Hebei 075000,China;Department of Blood Transfusion,the First Affiliated Hospital of Hebei North University,Zhangjiakou,Hebei 075000,China)

机构地区：[1]河北北方学院附属第一医院胸心血管外科,河北省张家口市075000 [2]河北北方学院附属第一医院急诊科,河北省张家口市075000 [3]河北北方学院附属第一医院放疗科,河北省张家口市075000 [4]河北北方学院附属第一医院输血科,河北省张家口市075000

出　　处：《中南医学科学杂志》2021年第6期668-671,702,共5页Medical Science Journal of Central South China

基　　金：河北省2021年度医学科学研究课题计划(20210266)。

摘　　要：目的探讨晚期非小细胞肺癌(NSCLC)患者肿瘤组织浸润巨噬细胞表面T细胞免疫球蛋白黏蛋白-3(Tim-3)表达特点,以及与其配体半乳凝素-9(Gal-9)组织表达、患者临床特征、预后的关系。方法选择80例晚期NSCLC组织和30例肺良性病变肺组织,采用免疫组织化学法和流式细胞术分别检测组织Tim-3和Gal-9蛋白表达量,以及肿瘤相关巨噬细胞(TAM)表面Tim-3表达,并分析HLA-DR^(+)TAM和CD163^(+)TAM表面Tim-3表达与组织Tim-3表达、Gal-9表达、临床特征、总生存期的关系。结果NSCLC组织Tim-3和Gal-9蛋白阳性表达率高于肺良性病变肺组织(P<0.05),且Tim-3在CD163^(+)TAM阳性表达率高于HLA-DR^(+)TAM(P<0.05)。NSCLC组织Gal-9蛋白表达与组织Tim-3蛋白表达呈正相关性(P<0.05)。HLA-DR^(+)TAM表面和CD163^(+)TAM表面Tim-3表达与患者肺外转移、TNM分期和2年生存预后有关(P<0.05)。HLA-DR^(+)TAM表面Tim-3蛋白高表达亚组患者总生存期长于低表达亚组(P=0.003),而CD163^(+)TAM表面Tim-3蛋白高表达亚组患者总生存期则短于低表达亚组(P=0.001)。结论晚期NSCLC组织中Tim-3和Gal-3均呈高表达,Tim-3/Gal-3信号通路在NSCLC肺外转移、疾病发展及预后不良中的作用可能与TAM向M2型巨噬细胞极化导致的肺癌炎症微环境有关。Aim To detect the expressions of T cell immunoglobulin domain and mucin domain(Tim-3)on the surface of tumor-associated macrophages(TAM)and its correlation with galectin-9(Gal-9)expression,pathological features and prognosis in patients with advancedadvanced non-small cell lung cancer(NSCLC).Methods Tissue samples from 80 advanced NSCLC patients and 30 patients with pulmonary benign diseases were collected into this study.Tim-3 and Gal-9 expressions in the tissues were detected by IHC and Tim-3 expressions on the surface of HLA-DR^(+)TAM or CD163^(+)TAM were detected by FCM.And their relationships with pathological features and death prognosis were analyzed.Results The positive rates of Tim-3 and Gal-9 proteins in NSCLC tissues were higher than those in pulmonary benign disease tissues(P<0.05),while Tim-3 expression on the surface of CD163^(+)TAM was higher than that on HLADR^(+)TAM(P<0.05).Gal-9 expressions in NSCLC tissues were positively related with Tim-3protein expression in NSCLC tissues(P<0.05).Besides,Tim-3 expressions on the surface of CD163^(+)TAM or HLA-DR^(+)TAM would be related with TNM stage,extrapulmonary metastasis and 2y-survival prognosis(P<0.05).The median overall survival of patients with higher Tim-3 expression on HLA-DR^(+)TAM was longer than that of patients with higher Tim-3 expression(P=0.003);and the median overall survival of patients with higher Tim-3 expression on CD163^(+)TAM was shorter than that of patients with lower Tim-3 expression(P=0.001).Conclusions In advanced NSCLC patients,Tim-3 and Gal-9 proteins levels in NSCLC tissues would increase,and be related with TNM stage,extrapulmonary metastasis and poor prognosis.The possible mechanism may be the inflammatory effect of Tim-3/Gal-9 pathway for the M2 polarization of TAM in the tumor microenviroment.

关 键 词：晚期非小细胞肺癌 肿瘤相关巨噬细胞 TIM-3 Gal-9 

分 类 号：R734.2[医药卫生—肿瘤]