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Cellular and gene signatures of tumor-infiltrating dendritic cells and natural-killer cells predict prognosis of neuroblastoma
Nature Communications ( IF 14.7 ) Pub Date : 2020-11-25 , DOI: 10.1038/s41467-020-19781-y
Ombretta Melaiu 1 , Marco Chierici 2 , Valeria Lucarini 1 , Giuseppe Jurman 2 , Libenzio Adrian Conti 3 , Rita De Vito 4 , Renata Boldrini 4 , Loredana Cifaldi 5 , Aurora Castellano 1 , Cesare Furlanello 2, 6 , Vincenzo Barnaba 7, 8 , Franco Locatelli 1, 9 , Doriana Fruci 1
Affiliation  

Tumor-infiltrating lymphocytes play an essential role in improving clinical outcome of neuroblastoma (NB) patients, but their relationship with other tumor-infiltrating immune cells in the T cell-inflamed tumors remains poorly investigated. Here we show that dendritic cells (DCs) and natural killer (NK) cells are positively correlated with T-cell infiltration in human NB, both at transcriptional and protein levels, and associate with a favorable prognosis. Multiplex imaging displays DC/NK/T cell conjugates in the tumor microenvironment of low-risk NB. Remarkably, this connection is further strengthened by the identification of gene signatures related to DCs and NK cells able to predict survival of NB patients and strongly correlate with the expression of PD-1 and PD-L1. In summary, our findings unveil a key prognostic role of DCs and NK cells and indicate their related gene signatures as promising tools for the identification of clinical biomarkers to better define risk stratification and survival of NB patients.



中文翻译:

肿瘤浸润树突状细胞和自然杀伤细胞的细胞和基因特征预测神经母细胞瘤的预后

肿瘤浸润淋巴细胞在改善神经母细胞瘤(NB)患者的临床结局中起着至关重要的作用,但是在T细胞炎性肿瘤中,它们与其他肿瘤浸润免疫细胞的关系仍然缺乏研究。在这里,我们显示树突状细胞(DCs)和自然杀伤(NK)细胞在转录水平和蛋白质水平均与人NB中的T细胞浸润呈正相关,并与良好的预后相关。多重成像显示低风险NB肿瘤微环境中的DC / NK / T细胞偶联物。值得注意的是,通过鉴定与DC和NK细胞有关的基因标记,可以进一步加强这种联系,这些基因能够预测NB患者的生存并与PD-1和PD-L1的表达密切相关。综上所述,

更新日期:2020-11-26
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