Peng Juan, Ding Tong, Zheng Li-Ming, Shao Jian-Yong
State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, 510060, P. R. China.
Ai Zheng. 2006 Nov;25(11):1340-5.
BACKGROUND & OBJECTIVE: Tumor-associated macrophages (TAMs) density is negatively correlated to prognosis of lung cancer, breast cancer, and so on, and positively correlated to prognosis of gastric cancer and some colorectal cancer. This study was to investigate the influence of TAMs on the progression and prognosis of nasopharyngeal carcinoma (NPC).
Immunohistochemistry was adopted to detect the expression of CD68, a marker of TAMs, in 60 specimens of NPC. Macrophages were cocultured respectively with supernatant liquid of NPC cell lines CNE-1 and CNE-2 and lung cancer cell line 95D for 1 day or 6 days, and then activated by LPS for 1 day. The expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10), secreted by TAMs after coculture of TAMs and supernatant liquid of NPC cell lines CNE-1 and CNE-2, was detected by ELISA. The macrophages co-cultured with supernatant of lung cancer cell line 95D was used as positive control; normal macrophages were used as negative control.
The 3-year tumor-freely survival rate was significantly higher in high TAMs density group than in low TAMs density group (85.7% vs. 56.3%, P<0.05). After coculture, the expression levels of TNF-alpha and IL-10 in supernatant were lower in CNE-1 group and CNE-2 group than in 95D group (73 pg/ml, 64 pg/ml vs. 7,794 pg/ml, P=0.001; 1 pg/ml, 1 pg/ml vs. 94 pg/ml, P=0.002); after LPS activation, the expression levels of TNF-alpha and IL-10 were higher in CNE-1 group and CNE-2 group than in 95D group (6,905 pg/ml, 6,788 pg/ml vs. 137 pg/ml, P=0.001; 87 pg/ml, 99 pg/ml vs. 416 pg/ml, P=0.015). But the difference between NPC cell lines and normal macrophages was not significant.
TAMs density is positively correlated to the prognosis of NPC. The cytokines secreted by TAMs trend to kill tumor cells and promote antitumor immune response.
肿瘤相关巨噬细胞(TAMs)密度与肺癌、乳腺癌等的预后呈负相关,与胃癌及部分结直肠癌的预后呈正相关。本研究旨在探讨TAMs对鼻咽癌(NPC)进展及预后的影响。
采用免疫组织化学法检测60例NPC标本中TAMs标志物CD68的表达。将巨噬细胞分别与NPC细胞系CNE-1和CNE-2以及肺癌细胞系95D的上清液共培养1天或6天,然后用脂多糖(LPS)激活1天。采用酶联免疫吸附测定法(ELISA)检测TAMs与NPC细胞系CNE-1和CNE-2上清液共培养后TAMs分泌的肿瘤坏死因子-α(TNF-α)和白细胞介素-10(IL-10)的表达。将与肺癌细胞系95D上清液共培养的巨噬细胞作为阳性对照;正常巨噬细胞作为阴性对照。
高TAMs密度组的3年无瘤生存率显著高于低TAMs密度组(85.7%对56.3%,P<0.05)。共培养后,CNE-1组和CNE-2组上清液中TNF-α和IL-10的表达水平低于95D组(73 pg/ml,64 pg/ml对7794 pg/ml,P=0.001;1 pg/ml,1 pg/ml对94 pg/ml,P=0.002);LPS激活后,CNE-1组和CNE-2组TNF-α和IL-10的表达水平高于95D组(6905 pg/ml,6788 pg/ml对137 pg/ml,P=0.001;87 pg/ml,99 pg/ml对416 pg/ml,P=0.015)。但NPC细胞系与正常巨噬细胞之间的差异不显著。
TAMs密度与NPC的预后呈正相关。TAMs分泌的细胞因子倾向于杀伤肿瘤细胞并促进抗肿瘤免疫反应。