Distinct signatures of the immune responses in low risk versus high risk neuroblastoma
Distinct signatures of the immune responses in low risk versus high risk neuroblastoma
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DOI：
10.1186/1479-5876-9-170
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发表时间：
2011-10-06
影响因子：
7.4
通讯作者：
Manjili, Masoud H.
中科院分区：
文献类型：
--
作者：
Gowda, Madhu;Godder, Kamar;Manjili, Masoud H.
背景：超过90%的低危(LR)神经母细胞瘤患者存活，而不到30%的高危(HR)患者长期存活。年龄(小于18个月的儿童)与LR病有关。考虑到获得性免疫系统在年龄较大的儿童中发育良好，而且T细胞被证明参与肿瘤逃逸和癌症的进展，我们试图确定与T细胞反应减弱但天然免疫反应完整的LR患者相比，HR患者是否倾向于表现出适应性免疫反应的特征。用流式细胞仪检测血液中的细胞成分，用多重细胞因子芯片检测患者血清中的细胞因子谱。HR肿瘤细胞株SK-N-SH也被用来检测对参与天然免疫反应的细胞因子IL-1β的反应。结果：HR和LR患者的基因表达模式不同，分别表明T细胞反应活跃和获得性免疫反应减弱。LR患者的获得性免疫反应明显减弱，表现为血清中IL-10水平较高。此外，与对照组LR患者相比，HR患者的循环髓系衍生抑制细胞(MDSC)水平较低。LR患者的先天免疫反应的细胞因子水平略高。结论：获得性免疫反应可能在HR疾病的发生发展中起重要作用，而LR患者的先天免疫反应可能是活跃的。
Background: Over 90% of low risk (LR) neuroblastoma patients survive whereas less than 30% of high risk (HR) patients are long term survivors. Age (children younger than 18 months old) is associated with LR disease. Considering that adaptive immune system is well developed in older children, and that T cells were shown to be involved in tumor escape and progression of cancers, we sought to determine whether HR patients may tend to show a signature of adaptive immune responses compared to LR patients who tend to have diminished T-cell responses but an intact innate immune response.Methods: We performed microarray analysis of RNA extracted from the tumor specimens of HR and LR patients. Flow cytometry was performed to determine the cellular constituents in the blood while multiplex cytokine array was used to detect the cytokine profile in patients' sera. A HR tumor cell line, SK-N-SH, was also used for detecting the response to IL-1 beta, a cytokines which is involved in the innate immune responses.Results: Distinct patterns of gene expression were detected in HR and LR patients indicating an active T-cell response and a diminished adaptive immune response, respectively. A diminished adaptive immune response in LR patients was evident by higher levels of IL-10 in the sera. In addition, HR patients had lower levels of circulating myeloid derived suppressor cells (MDSC) compared with a control LR patient. LR patients showed slightly higher levels of cytokines of the innate immune responses. Treatment of the HR tumor line with IL-1b induced expression of cytokines of the innate immune responses.Conclusions: This data suggests that adaptive immune responses may play an important role in the progression of HR disease whereas innate immune responses may be active in LR patients.