肿瘤相关巨噬细胞对鼻咽癌进展和预后的影响

背景与目的:有研究表明,在肺癌、乳腺癌等肿瘤组织中,肿瘤相关巨噬细胞(tumor-associatedmacrophages,TAMs)与肿瘤的预后呈负相关。然而在胃癌和部分结直肠癌的研究中得出了TAMs与预后呈正相关的结论。本研究旨在探讨TAMs对鼻咽癌(nasopharyngealcarcinoma,NPC)进展和预后的影响。方法:应用免疫组化技术检测60例鼻咽癌组织中TAMs标记物CD68的表达;分别培养正常巨噬细胞、鼻咽癌细胞株CNE-1和CNE-2以及肺癌细胞株95D,将同浓度的3种癌细胞株的上清液加入同量的巨噬细胞中共培养1天,6天及加入LPS活化后继续培养1天,应用ELISA技术检测共培养后TAMs释放的细胞因子TNF-α和IL-10的表达。以与肺癌细胞株95D上清液共培养后的巨噬细胞作为阳性对照;正常巨噬细胞作为阴性对照。结果:鼻咽癌组织中TAMs高密度表达者的3年无瘤生存率(85.7%)明显高于低密度表达者(56.3%)(P=0.017)。与阳性对照组比较,接受鼻咽癌细胞株CNE-1和CNE-2上清液刺激后的TAMs分泌TNF-α较少(73pg/ml,64pg/mlvs.7794pg/ml,P=0.001),经LPS活化后明显增多(6905pg/ml,6788pg/mlvs.137pg/ml,P=0.001);分泌IL-10很少(1pg/ml,1pg/mlvs.94pg/ml,P=0.002),经LPS活化后升高不明显(87pg/ml,99pg/mlvs.416pg/ml,P=0.015),与阴性对照组比较差异无显著性。结论:鼻咽癌组织中TAMs的密度与患者的预后呈正相关;与鼻咽癌细胞上清液共培养后TAMs分泌的细胞因子倾向于杀伤肿瘤细胞,促进机体的抗瘤免疫作用。

Influence of tumor-associated macrophages on progression and prognosis of nasopharyngeal carcinoma

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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.