Co-culture of head and neck squamous cell carcinoma spheroids with autologous monocytes predicts prognosis

Co-culture of head and neck squamous cell carcinoma spheroids with autologous monocytes predicts prognosis
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DOI:
10.1111/j.1365-3083.2008.02072.x
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发表时间:
2008-04-01
影响因子:
3.7
通讯作者:
Aarstad, H. J.
Aarstad, H. J.
中科院分区:
医学4区
文献类型:
--
作者:
Kross, K. W.;Heimdal, J. H.;Aarstad, H. J.

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头颈部鳞状细胞癌(HNSCC)的单核细胞与来自恶性(M)肿瘤或良性(B)对照粘膜的自体碎片(F)球体共培养产生IL-6和单核细胞趋化蛋白(MCP)-1分泌。本研究探讨这种细胞因子共培养反应与预后之间的关系。对1998年至2005年间确诊的65例HNSCC患者进行了单核细胞与自体MF或BF球体体外共培养上清液中IL-6和MCP-1含量的分析。IL-6反应被表达为同一批单核细胞脂多糖反应的一部分。2005年下半年之后,复发率、存活率和死因得以确定。单核细胞趋化蛋白-1水平不能预测预后。我们发现,自体单核细胞IL-6水平升高预测复发,风险比(HR)为1.5[可信区间(CI):1.0 1~2.6 0;P=0.0 5],与BF球体和单核细胞共培养预测复发(HR=4.17;CI:1.5 4~11.29;P=0.005)。与患者的TNM分期结果相同。同时分析BF和MF球体共培养的IL-6反应,以及调整患者的年龄和TNM分期,可以根据BF共培养水平预测总生存期(HR=3.1;CI:1.11-8.56;P=0.03)。与单核细胞和BF球体体外共培养产生的IL-6可预测复发和预后,而与单核细胞和MF球体共培养可预测复发。
Co-culture of monocytes with autologous fragment (F) spheroids originating from malignant (M) tumour or benign (B) control mucosa of head and neck squamous cell carcinoma (HNSCC) yields interleukin (IL)-6 and monocyte chemo-attractant protein (MCP)-1 secretion. This study investigates the association between this cytokine co-culture response and prognosis. Analysis of IL-6 and MCP-1 content of supernatants from monocytes in vitro co-culture with autologous MF- or BF-spheroids was investigated in a cohort of HNSCC patients (n = 65) diagnosed between 1998 and 2005, all of whom were treated with curative intent by primary surgery. The IL-6 response was expressed as a fraction of the lipopolysaccharid response of the same batch of monocytes. Recurrence, survival and causes of death were then established following the second part of 2005. MCP-1 levels did not predict prognosis. We found that increased levels of IL-6 from autologous monocytes in co-culture with MF-spheroids predicted recurrence with a hazard ratio (HR) of 1.5 [confidence interval (CI): 1.01-2.60; P = 0.05] and co-culture with BF-spheroids and monocytes predicted recurrence (HR = 4.17; CI: 1.54-11.29; P = 0.005). The same results where obtained in addition with TNM stage of the patients. Simultaneous analysis of BF- and MF-spheroid co-culture IL-6 responses as well as adjustment for age and TNM stage of the patients allowed prediction of total survival (HR = 3.1; CI: 1.11-8.56; P = 0.03) based on BF co-culture levels. IL-6 secreted upon in vitro co-culture with monocytes and BF-spheroids predicts recurrence and prognosis, whereas co-culture with monocytes and MF-spheroids predicts recurrence.