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Prognostic profiling of the immune cell microenvironment in Ewing´s Sarcoma Family of Tumors.
OncoImmunology ( IF 7.2 ) Pub Date : 2019-10-13 , DOI: 10.1080/2162402x.2019.1674113
David Stahl 1 , Andrew J Gentles 2 , Ralf Thiele 3 , Ines Gütgemann 1
Affiliation  

Ewing´s Sarcoma Family of Tumors (ESFT) are clinically aggressive bone and soft tissue tumors in children and young adults. Analysis of the immune tumor microenvironment (TME) provides insight into tumor evolution and novel treatment options. So far, the scarcity of immune cells in ESFT has hindered a comprehensive analysis of rare subtypes. We determined the relative fraction of 22 immune cell types using 197 microarray gene expression datasets of primary ESFT tumor samples by using CIBERSORT, a deconvolution algorithm enumerating infiltrating leucocytes in bulk tumor tissue. The most abundant cells were macrophages (mean 43% of total tumor-infiltrating leukocytes, TILs), predominantly immunosuppressive M2 type macrophages, followed by T cells (mean 23% of TILs). Increased neutrophils, albeit at low number, were associated with a poor overall survival (OS) (p = .038) and increased M2 macrophages predicted a shorter event-free survival (EFS) (p = .033). High frequency of T cells and activated NK cells correlated with prolonged OS (p = .044 and p = .007, respectively). A small patient population (9/32) with combined low infiltrating M2 macrophages, low neutrophils, and high total T cells was identified with favorable outcome. This finding was confirmed in a validation cohort of patients with follow up (11/38). When comparing the immune TME with expression of known stemness genes, hypoxia-inducible factor 1 α (HIF1α) correlated with high abundance of macrophages and neutrophils and decreased T cell levels. The immune TME in ESFTs shows a distinct composition including rare immune cell subsets that in part may be due to expression of HIF1α.

中文翻译:

尤因氏肉瘤家族中免疫细胞微环境的预后分析。

尤因氏肉瘤家族(ESFT)是儿童和年轻人中具有临床侵袭性的骨和软组织肿瘤。免疫肿瘤微环境(TME)的分析可洞悉肿瘤的进展和新颖的治疗选择。迄今为止,ESFT中免疫细胞的缺乏已经阻碍了对稀有亚型的全面分析。我们使用CIBERSORT(一种枚举大块肿瘤组织中浸润白细胞的反卷积算法),使用原发ESFT肿瘤样品的197个微阵列基因表达数据集确定了22种免疫细胞类型的相对分数。最丰富的细胞是巨噬细胞(占肿瘤浸润白细胞总数的43%,TILs),主要是免疫抑制性M2型巨噬细胞,其次是T细胞(占TILs的23%)。中性粒细胞增加,尽管数量很少,P = .038)和增加的M2巨噬细胞预测较短的无事件生存期(EFS)(p = .033)。T细胞和活化NK细胞的高频率与OS延长有关(p = .044和p分别为.007)。少数患者(9/32)合并低浸润性M2巨噬细胞,低嗜中性粒细胞和高总T细胞,具有良好的预后。一项随访患者的验证队列证实了这一发现(11/38)。将免疫TME与已知干基因的表达进行比较时,缺氧诱导因子1α(HIF1α)与巨噬细胞和中性粒细胞的丰度高和T细胞水平降低有关。ESFTs中的免疫TME显示出独特的组成,包括稀有的免疫细胞亚群,部分是由于HIF1α的表达。
更新日期:2019-10-25
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