肺癌围手术期髓系抑制细胞的变化及对肿瘤生长和血管生成的影响  

Changes of myeloid-derived suppressor cells during perioperative period in patients with lung cancer and its influence on tumor growth and angiogenesis in vivo

作　　者：汪珺[1] 苏晓三[2] 乔飞[1] 杨柳[2] 王益寅 尹燕锋[2] 洪志鹏[3] 

机构地区：[1]昆明医科大学第一附属医院麻醉科,云南昆明650031 [2]昆明市第一人民医院(昆明医科大学附属甘美医院)生物医学实验中心,云南昆明650011 [3]昆明医科大学第一附属医院胸外科,云南昆明650031

出　　处：《肿瘤》2016年第4期452-458,473,共8页Tumor

基　　金：国家自然科学基金项目(编号:31360223)~~

摘　　要：目的:检测肺癌围手术期外周血髓系抑制细胞(myeloid-derived suppressor cells,MDSCs)的变化,并探讨其对肿瘤生长和肿瘤血管生成的影响。方法:采用FCM和血细胞分析技术检测98例肺癌患者围手术期外周血单个核细胞(peripheral blood mononuclear cells,PBMCs)中CD11b^+CD33^+HLA-DR^-细胞百分比和浓度,蛋白芯片和ELISA检测血清中细胞因子的浓度。将围手术期CD11b^+CD33^+人类白细胞抗原DR(human leukocyte antigen-DR,HLA-DR)^-细胞和人肺腺癌细胞A549接种至裸鼠皮下,观察其对肿瘤生长和肿瘤血管生成的影响。结果:肺癌患者术后PBMCs中CD11b^+CD33^+HLA-DR-细胞百分比和浓度均较术前显著升高(P值均<0.05);外周血清CXC趋化因子配体5(CXC chemokine ligand 5,CXCL5)、单核细胞趋化蛋白1(monocyte chemoattractant protein-1,MCP-1)、巨噬细胞炎性蛋白1α(macrophage infl ammatory protein-1α,MIP-1α)/MIP-1β和MIP-3α等趋化因子以及血管内皮生长因子(vascular endothelial growth factor,VEGF)的浓度均较术前显著升高(P值均<0.05)。裸鼠致瘤能力观察结果显示,术后MDSCs促肿瘤生长和肿瘤血管生成的能力较术前MDSCs显著增强(P值均<0.05)。结论:肺癌患者术后PBMCs中MDSCs较术前增加,且其促肿瘤血管生成和肿瘤生长的作用增强,提示MDSCs可能成为预防肿瘤术后转移的新靶点。Objective：To evaluate the changes of myeloid-derived suppressorcells（MDSCs） in perioperative period in lung cancer patients and its influence on tumor growth and angiogenesis.Methods：The percentage and concentration of MDSCs in peripheral blood mononuclear cells（PBMCs） were detected during perioperative period by flow cytometry and blood cell analysis in 98 patients with lung cancer.The concentrations of various cytokines in serum were also detected using cytokine array and enzyme-linked immunosorbent assay（ELISA）.To observe the influence of CD11b~＋CD33~＋ human leukocyte antigen-DR（HLA-DR）^-cells on tumor growth and angiogenesis,human lung cancer A549 cells combined with perioperative isolated CD11b~＋CD33~＋HLA-DR^-cells were injected subcutaneously into nude mice.Results：Either the percentage or the concentration of CD11b~＋CD33~＋HLA-DR-cells significantly increased in lung cancer patients after surgery as compared with pre-operation.Compared with pre-operation,the concentrations of chemokines such as CXC chemokine ligand 5（CXCL5）,monocyte chemoattractant protein-1（MCP-1）,macrophage inflammatory protein-1α（MIP-1α）/MIP-1β and MIP-3α and pro-angiogenic cytokine vascular endothelial growth factor（VEGF） in serum were increased in postoperative period（all P 〈0.05）.Isolated MDSCs after surgery were more efficient in promoting angiogenesis and tumor growth than MDSCs isolated before surgical operation in xenograft tumor model（both P 〈0.05）.Conclusion：Postoperatively induced MDSCs are significantly increased and qualified with potent pro-angiogenic and tumor promotive ability.This cell population should be considered as a target for preventing post-operative tumor metastasis.

关 键 词：肺肿瘤 围手术期 细胞免疫 髓系细胞 

分 类 号：R734.2[医药卫生—肿瘤]