Immunogenomic landscape of gynecologic carcinosarcoma
Immunogenomic landscape of gynecologic carcinosarcoma
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DOI：
10.1016/j.ygyno.2020.11.030
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发表时间：
2021-01-23
影响因子：
4.7
通讯作者：
Mori, Seiichi
中科院分区：
文献类型：
--
作者：
Gotoh, Osamu;Kiyotani, Kazuma;Mori, Seiichi
objective.子宫或卵巢癌肉瘤是一种罕见的双相肿瘤，由上皮细胞和间质细胞组成，其临床特征比癌更具侵袭性。最近基于基因组畸变谱（POLE、MSI、CNH和CNL）确定了CS的四种分子亚型，并显示与多种临床病理学参数（包括患者结局）相关。然而，免疫微环境在CS中的作用仍不清楚。在这里，我们调查的免疫细胞浸润CS的影响，以更好地了解妇科CS的免疫状态。使用RNA-seq的免疫细胞谱分析、微环境基因的转录组学亚型分析和T细胞受体库测定对CS样品进行肿瘤免疫微环境分析。CS样本中的癌和肉瘤成分也分别进行了评估。根据RNA-seq数据对肿瘤浸润细胞类型的估计，POLE和MSI（超变）肿瘤显示M1巨噬细胞、浆细胞和CD8（+）T细胞富集，而CNH和CNL（非超变）肿瘤具有高水平的M2巨噬细胞。通过免疫相关的非癌基因的进一步亚分类，确定了一部分具有不同患者结局的肿瘤，特别是具有CNH基因组畸变亚型的肿瘤。T细胞异质性与无进展生存期延长独立相关。癌和肉瘤成分的差异分析鉴定了许多共有的突变，但两种成分之间的T细胞受体库几乎没有重叠。肿瘤免疫微环境分析可以提供潜在的临床实用性，在妇科CS的分层以上单独的基因组畸变亚型的分类。(c)2020爱思唯尔公司All rights reserved.
Objective. Carcinosarcoma (CS) of the uterus or ovary isa rare, biphasic tumor comprising epithelial and mesenchymal elements, and exhibits more aggressive clinical features than its carcinoma counterpart. Four molecular subtypes of CS were recently established based on genomic aberration profiles (POLE, MSI, CNH, and CNL) and shown to be associated with multiple clinicopathological parameters, including patient outcomes. However, the role of the immune microenvironment in CS remains unclear. Here, we investigated the influence of the immune cells that infiltrate CS to better understand the immunological status of gynecological CS.Methods. Tumor immune microenvironmental analyses on CS samples were performed using immune cell profiling with RNA-seq, transcriptomic subtyping with microenvironmental genes, and T-cell receptor repertoire assay. Carcinoma and sarcoma elements from CS samples were also assessed separately.Results. Relying on estimations of tumor-infiltrating cell types from RNA-seq data, POLE and MSI (hypermutator) tumors showed an enrichment of M1 macrophages, plasma cells and CD8(+) T cells, whereas CNH and CNL (non-hypermutator) tumors had high levels of M2 macrophages. Further subclassification by immune-related, non-cancer genes identified a fraction of tumors with distinct patient outcomes, particularly those with the CNH genomic aberration subtype. T-cell heterogeneity was independently correlated with prolonged progression-free survival. Differential analysis of carcinoma and sarcoma elements identified many shared mutations but there was little overlap in the T-cell receptor repertoire between the two elements.Conclusions. Tumor immune microenvironmental analyses could offer potential clinical utility in the stratification of gynecological CS above classification by genomic aberration subtype alone. (c) 2020 Elsevier Inc. All rights reserved.