Zhang Peng, Wu Xiaofang, Basu Moushumi, Dong Chen, Zheng Pan, Liu Yang, Sandler Anthony David
Center for Cancer and Immunology Research, Children's National Health System, Washington, DC, United States.
Sheikh-Zayed Institute for Pediatric Surgical Innovation, Children's National Health System, Washington, DC, United States.
Front Immunol. 2017 Nov 3;8:1473. doi: 10.3389/fimmu.2017.01473. eCollection 2017.
RNA and DNA sequencing data are traditionally used to discern intrinsic cellular pathways in cancer pathogenesis, their utility for investigating the tumor microenvironment (TME) has not been fully explored. This study explores the use of sequencing data to investigate immunity within the TME.
Here, we use immune cell fraction estimation analysis to determine the immune profiles in the microenvironment of neuroblastoma (NB) based on RNA-seq data in the TARGET database. The correlation between immune cell transcripts and prognosis in pediatric NB is also investigated.
analysis revealed a strong inverse correlation between amplification and leukocyte infiltration. This finding was validated by immunohistochemistry analysis in tumor samples. Moreover, the abundance of CD4 T cells strongly associated with better patient survival regardless of gene amplification, while those of CD8 T cells, NK or B cells do not. Based on characteristic cytokine expression of CD4 subsets in tumors, the Th2 rather than Th1 levels were associated with better prognosis.
We found that the analysis of TARGET database reflected tumor immunity and was validated by the immunohistochemical tumor data. Our results reveal the association of amplification with repressed cellular immunity and the potential prognostic value of infiltrating CD4 T cell transcripts in pediatric NB. This analysis illustrates the potential role of in NB as a regulator of immune privilege and characterizes the power of analysis for delineating cancer immunology and risk stratification.
RNA和DNA测序数据传统上用于识别癌症发病机制中的内在细胞通路,但其在研究肿瘤微环境(TME)方面的效用尚未得到充分探索。本研究探讨了利用测序数据研究TME中的免疫情况。
在此,我们基于TARGET数据库中的RNA测序数据,使用免疫细胞分数估计分析来确定神经母细胞瘤(NB)微环境中的免疫谱。还研究了小儿NB中免疫细胞转录本与预后之间的相关性。
分析显示 扩增与白细胞浸润之间存在强烈的负相关。这一发现通过肿瘤样本的免疫组织化学分析得到验证。此外,无论基因扩增情况如何,CD4 T细胞的丰度与患者更好的生存率密切相关,而CD8 T细胞、NK细胞或B细胞的丰度则不然。基于肿瘤中CD4亚群的特征性细胞因子表达,Th2而非Th1水平与更好的预后相关。
我们发现对TARGET数据库的分析反映了肿瘤免疫情况,并通过肿瘤免疫组织化学数据得到验证。我们的结果揭示了 扩增与细胞免疫抑制之间的关联以及小儿NB中浸润性CD4 T细胞转录本的潜在预后价值。该分析说明了 在NB中作为免疫特权调节因子的潜在作用,并表征了 分析在描绘癌症免疫学和风险分层方面的作用。