胆管癌患者外周血免疫抑制细胞的检测及其临床意义  

Detection and Clinical Analysis of Myeloid Derived Suppressor Cells of Peripheral Blood in Patients with Cholangiocarcinoma

作　　者：徐晓东[1] 王敏[1] 田锐[1] 李旭[1] 郭兴军[1] 彭丰[1] 胡均[2] 秦仁义[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院胆胰外科,武汉430030 [2]天津医科大学附属肿瘤研究所、肿瘤医院结肠癌外科、国家临床肿瘤研究中心、癌症预防和治疗重点实验室,天津300060

出　　处：《华中科技大学学报（医学版）》2015年第4期424-428,共5页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金资助项目(No.81101870,No.81402443)

摘　　要：目的研究胆管癌患者外周血中CD14+CD11b+HLA-DR-髓源性抑制细胞(MDSC)的表达及其与临床分期和术后病理检测的关系,并对其形成机制和功能进行初步研究。方法采用流式细胞术检测了25例胆管癌、10例胰腺癌、9例胆囊癌患者和25例同龄的健康对照者外周血中CD14+CD11b+HLA-DR-髓源性抑制细胞的比例并进行统计学分析。结果健康成人对照组外周血中CD14+CD11b+HLA-DR-MDSC的比例为(0.65±0.25)%,胆管癌组患者比例显著增高为(2.14±1.38)%,两组比较差异有统计学意义(P<0.05)。同时,在胰腺癌组和胆囊癌组患者中MDSC的表达水平亦升高。MDSC的表达水平与胆管癌的临床分期相关,其中Ⅳ期胆管癌患者的MDSC水平最高。胆管癌患者术后的MDSC水平较术前显著降低,差异有统计学意义(P<0.01)。但是,MDSC的表达水平与胆管癌患者术后的病理分期无关。两种胆管癌细胞系(QBC939、TFK-1)体外均能诱导PBMC向MDSC的转化,且随着肿瘤负荷的增加而增加。和健康对照组比,胆管癌患者外周血中发挥抑制功能的精氨酸酶活性增加,两组比较差异有统计学意义(P<0.05)。结论胆管癌患者外周血中CD14+CD11b+HLA-DR-MDSC的比例显著升高,且与肿瘤的临床分期呈正相关,可作为胆管癌患者早期诊断的重要标记物。Objective To study expression level of CD14＋CD11b＋HLA-DR-myeloid derived suppressor cells in peripheral blood of patients with cholangiocarcinoma,and relationship between the expression and clinical stage,pathological grade,and to preliminarily investigate the mechanisms.Methods From 25 cholangiocarcinoma patients,10 pancreatic cancer patients,9gallbladder carcinoma patients and 26age-matched healthy controls,CD14＋CD11b＋HLA-DR-myeloid derived suppressor cells were collected from peripheral blood and analyzed by flow cytometry.Results Proportion of yeloid derived suppressor cells of normal healthy group was（0.65±0.25）%,and（2.14±1.38）%for bile duct cancer group,with significant difference（P〈0.05）.Meanwhile,elevated levels of MDSC were also detected in pancreatic cancer and gallbladder cancer.Expression level of MDSC was correlated with clinical stages of cholangiocarcinoma,and it was highest in IV stage patients.After radical operation,MDSC level decreased significantly in cholangiocarcinoma patients（P〈0.05）.However,MDSC level was not related with pathological stage of cholangiocarcinoma patients after surgery.Two cholangiocarcinoma cell lines could successfully induce PBMC to transform into MDSCin vitro,and the transformation was increased with tumor burden.Critical suppressive enzyme arginase was significantly more active in cholangiocarcinoma patients than in control group（P〈0.05）.Conclusion Proportion of myeloid derived suppressor cell level in cholangiocarcinoma patients are significantly elevated and positively related with clinical stages,and it can be used as an early marker for detection of cholangiocarcinoma.

关 键 词：胆管癌 髓源性免疫抑制细胞 精氨酸酶 

分 类 号：R735.8[医药卫生—肿瘤]