非霍奇金淋巴瘤患者外周血髓样抑制细胞的鉴定及其临床意义  

Identification of myeloid-derived suppressor cells in peripheral blood of patients with non-Hodgkin lymphoma and its clinical significance

作　　者：鲍慧铮[1] 田甜[2] 刘岩[2] 赵丹丹[2] 于昊[1] 徐娜[1] 李慧[2] 

机构地区：[1]吉林省肿瘤医院淋巴血液科,长春130012 [2]吉林省肿瘤医院肿瘤转化医学实验室,长春130012

出　　处：《白血病．淋巴瘤》2018年第2期83-88,共6页Journal of Leukemia & Lymphoma

基　　金：吉林省卫生和计划生育委员会科研计划（20142020、2017J026）

摘　　要：目的 探讨非霍奇金淋巴瘤（NHL）患者外周血中髓样抑制细胞（MDSC）的表达情况及其临床意义.方法 收集2014年1月至2015年2月吉林省肿瘤医院69例NHL患者和21名健康人外周血,采用流式细胞术,通过抗CD11b、CD33、CD14、人类白细胞抗原（HLA）-DR等不同荧光抗体组合来鉴定MDSC的细胞表面标志,应用免疫磁珠技术富集MDSC后采用实时荧光定量聚合酶链反应（qRT-PCR）检测精氨酸酶1（Arg-1）、诱导型一氧化氮合酶（iNOS）和环氧合酶2（COX-2）的表达,采用体外增殖实验检测T细胞功能,分析MDSC水平与NHL患者临床病理特征的相关性.应用t检验和方差分析统计数据.结果NHL患者外周血中存在高水平的CD11b＋CD14＋CD33＋细胞群,细胞形态属于单个核细胞.NHL患者和健康对照组CD11b＋CD14＋CD33＋MDSC比例分别为（42±10）％和（34±11）％,差异具有统计学意义（t=0.300,P=0.005）.CD11b＋CD14＋CD33＋细胞和CD11b＋CD14＋CD33-细胞中Arg-1、COX-2和iNOS的相对表达量分别为0.12±0.04和1.00±0.25（t=6.095,P=0.024）,3.03±0.45和1.00±0.78（t=7.766,P=0.016）,0.29±0.11和1.00±0.04（t=1.987,P=0.209）.该群细胞具有抑制T细胞增殖的能力.MDSC在不同国际预后指数（IPI）评分的患者中表达水平差异有统计学意义（F=2.536,P=0.049）,在不同性别、年龄、病理类型、临床分期、血清乳酸脱氢酶、体力状况评分及β2微球蛋白的患者中表达水平差异均无统计学意义（均P〈0.05）.结论NHL患者外周血中存在高水平CD11b＋CD14＋CD33＋细胞,表达髓样细胞特征性蛋白,具有抑制T细胞增殖的功能,符合MDSC特性,其水平与IPI评分有关.MDSC可能作为一种新的生物标志物用于NHL临床实践.Objective To explore the presence of myeloid-derived suppressor cells （MDSC） in patients with non-Hodgkin lymphoma （NHL） and its clinical value. Methods Peripheral blood samples were collected from 69 NHL patients and 21 healthy controls admitted in Jilin Cancer Hospital from January 2014 to February 2015. Flow cytometry was conducted to identify unique cell surface markers of MDSC using antibodies against CD11b, CD33, CD14 or HLA-DR. MDSC were enriched by immunomagnetic beads, then arginase 1 （Arg-1）, inducible nitric oxide synthase （iNOS） and cyclooxygenase 2 （COX-2） in which were detected by real time-PCR. In vitro, cell proliferation assay was used to test T cell function. Statistical analysis was used to explore the correlation between MDSC and clinical features. Results There were a high level of CD11b＋CD14＋CD33＋cells in peripheral blood of NHL patients. The morphology of the cells belonged to mononuclear cells. The ratio of monocytic CD11b＋CD14＋CD33＋cells in NHL patients was higher than those in healthy controls [（42±10） ％ vs. （34±11） ％, t= 0.300, P= 0.005]. The expressions of Arg-1, COX-2 and iNOS in CD11b＋CD14＋CD33＋and CD11b＋CD14＋CD33-cells were 0.12±0.04 vs. 1.00±0.25 （t= 6.095, P=0.024）, 3.03±0.45 vs. 1.00±0.78 （t= 7.766, P= 0.016） and 0.29±0.11 vs. 1.00±0.04 （t= 1.987, P= 0.209）, respectively. In addition, the CD11b＋CD14＋CD33＋cells inhibited T cell proliferation. The levels of MDSC in patients with different international prognostic index （IPI） score were significantly different （F= 2.536, P=0.049）, but the levels of MDSC in patients with different sex, age, pathological type, stage, serum lactate dehydrogenase, physical status staging criteria and β2-microglobulin had no differences （all P 〈 0.05）. Conclusions CD11b＋ CD14＋ CD33＋ cells are characterized as MDSC in terms of higher level in NHL patients, expressing myeloid-specific proteins, and inhibiting T cell proliferation. The expression of MDSC is

关 键 词：淋巴瘤 非霍奇金 髓样抑制细胞 抗原 分化 生物学鉴定法 

分 类 号：R733.1[医药卫生—肿瘤]