摘要
目的 建立免疫健全小鼠胰腺癌皮下种植瘤模型,利用该模型观察胰腺癌发展过程中CD11b^＋GR-1^＋髓系来源抑制细胞（MDSC）及其亚群CD11b^＋ Ly6CkwLy6G^＋粒细胞型MDSC（PMN-MDSC）及CD11b^＋ Ly6C^＋Ly6G^-单核细胞型MDSC（Mo-MDSC）,F4/80^＋肿瘤相关巨噬细胞（TAM）及其亚群F4/80^＋ CD16/32^＋ CD206-M1型TAM、F4/80^＋ CD16/32-CD206^＋ M2型TAM在外周血及肿瘤组织中的动态变化过程.方法 利用C57B6/J小鼠同源Panc02胰腺癌细胞建立皮下种植瘤模型.根据肿瘤大小将其分为T1 - T4期.利用流式细胞染色法观察外周血及肿瘤组织中上述免疫细胞群的动态变化过程.结果 随着胰腺癌进展,外周血及肿瘤组织中MDSC呈逐渐增多趋势[外周血T1比T4为（4.95±1.03）％比（36.45±6.43）％,P＜0.01;肿瘤组织T1比T4为（2.95±2.95）％比（18.17±3.30）％,P＜0.01];其中以PMN-MDSC增高为主[外周血T1比T4为（29.73±10.30）％比（66.40±12.10）％,P＜0.01;肿瘤组织T1比T4为（24.73±10.81）％比（73.17±10.81）％,P＜0.01],而Mo-MDSC无明显变化[外周血T1比T4为（10.30±1.90）％比（9.87±1.91）％,P＞0.05;肿瘤组织T1比T4为（9.10±1.01）％比（9.90±2.21）％,P＞0.05];T1 -T3期外周血M1及M2均增多[M1：T1比T3为（6.30±1.25）％比（20.17±2.31）％,P＜0.01;M2：T1比T3为（0.87±0.21）％比（5.40±0.85）％,P＜0.01],但M2/M1比值逐渐增大;T4期M1骤然减少[T3比T4为（20.17±2.31）％比（10.77±1.52）％,P＜0.01],但M2持续增多[T3比T4为（6.80±0.75）％比（8.97±1.20）％,P＜0.05],M2/M1比值进一步增大;T1- T4期肿瘤组织中M2持续增多[T1比T4为（2.94±0.51）％比（13.44±2.95）％,P＜0.01],M1无明显变化[T1比T4为（6.49±1.39）％比（7.26±1.96）％,P＞0.05],M2/M1比值明显大于同期肿瘤外周血.结论 外周血及肿瘤组织中PMN-MDSC×M2/M1可以有效地反映胰腺癌荷瘤鼠肿瘤负荷,有可能成为预测胰腺癌患者预后的有效指标.
Objective To establish an immunocompetent pancreatic cancer bearing mice model and clarify the dynamic changes of the CD11b＋ GR-1^ ＋ myeloid derived suppressor cells （MDSC）,CD11 b ^＋ Ly6Clow Ly6G^ ＋ polymorphonuclear myeloid derived suppressor cells （PMN-MDSC） and CD1 1b^ ＋ Ly6C ^＋ Ly6G-monocytic myeloid derived suppressor cells （Mo-MDSC）,F4/80^＋ tumor associated macrophages （TAM） and F4/80^ ＋ CD16/32^ ＋ CD206-classical activated macrophages （M1）,F4/80^ ＋ CD16/32-CD206^ ＋ adaptive activated macrophages （M2） in pancreatic cancer bearing mice.Methods The C57B6/J mice syngeneic pancreatic adenocarcinoma cell line Panc02 ceils were subcutaneously implanted to establish the immunocompetent murine pancreatic cancer bearing model.According to the tumor size,it was divided into four stages,named T1-T4.The flow cytometry （FCM） was performed to identify the different cell populations.Results With tumor progression,the MDSC population was consistently increased [for peripheral blood,T1 vs.T4,（4.95 ±1.03）% vs.（36.45 ±6.43）%,P〈0.01; for tumor tissue,T1 vs.T4,（2.95 ± 2.95） % vs.（18.17 ± 3.30） %,P 〈 0.01],and the PMN-MDSC was the main subpopulation and dramatically increased [for peripheral blood,T1 vs.T4,（29.73 ± 10.30） % vs.（66.40 ± 12.10）%,P〈0.01; for tumor tissue,T1 vs.T4,（24.73±10.81）% vs.（73.17±10.81）%,P〈 0.01],but the other subtype Mo-MDSC did not significantly change [for peripheral blood,T1 vs.T4,（10.30 ± 1.90） % vs.（9.87 ± 1.91） %,P 〉 0.05 ; for tumor tissue,T1 vs.T4,（9.10 ± 1.01） % vs.（9.90 ±2.21）%,P 〉0.05].The TAM in peripheral blood in T1-T3 stages was consistently increased,including both M1 and M2 [for M1,T1 vs.T3,（6.30 ± 1.25） % vs.（20.17 ±2.31） %,P 〈0.01 ; for M2,（0.87 ± 0.21） % vs.（5.40 ± 0.85） %,P 〈 0.01],but the M2/M1 ratio became bigger.The peripheral blood macrophages in T4 stage were dramatically declined [T3 vs.T4,（20.17 ± 2.31） % vs.（10.77 ± 1.52） %,P 〈0.01],but M2 was still increased [T3 vs.T4,（6.80 ± 0.75） % vs.（8.97 ± 1.20）%,P 〈0.05].The intratumoral M2 tumor associated macrophages were consistently increased [T1 vs.T4,（2.94 ±0.51）% vs.（13.44 ±2.95）%,P〈0.01],but the M1 did not significantly change [T1 vs.T4,（6.49 ± 1.39） % vs.（7.26 ± 1.96） %,P 〉 0.05].The ratio of M2/M1 was bigger than that of peripheral blood at the same stage.Conclusion The PMN-MDSC × M2/M1 ratio in peripheral blood and tumor tissue is the formidable surrogate for the tumor burden of pancreatic cancer bearing mice and can be used as a predictor for the prognosis of patients with pancreatic cancer.
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2014年第11期2430-2433,共4页
Chinese Journal of Experimental Surgery
基金
国家自然科学基金面上资助项目（81272573）
关键词
胰腺癌
髓系来源抑制细胞
肿瘤相关巨噬细胞
预后
Pancreatic cancer
Myeloid derived suppressor cells
Tumor associated macrophages
Prognosis
