Institut Curie, PSL University, INSERM U932, Immunity and Cancer, 75005 Paris, France.
Biological and Environmental Proteomics, Institut d'Investigacions Biomèdiques de Barcelona-CSIC, IDIBAPS, Roselló 161, 6a planta, 08036 Barcelona, Spain.
Cell Rep. 2022 Jun 7;39(10):110916. doi: 10.1016/j.celrep.2022.110916.
We analyze transposable elements (TEs) in glioblastoma (GBM) patients using a proteogenomic pipeline that combines single-cell transcriptomics, bulk RNA sequencing (RNA-seq) samples from tumors and healthy-tissue cohorts, and immunopeptidomic samples. We thus identify 370 human leukocyte antigen (HLA)-I-bound peptides encoded by TEs differentially expressed in GBM. Some of the peptides are encoded by repeat sequences from intact open reading frames (ORFs) present in up to several hundred TEs from recent long interspersed nuclear element (LINE)-1, long terminal repeat (LTR), and SVA subfamilies. Other HLA-I-bound peptides are encoded by single copies of TEs from old subfamilies that are expressed recurrently in GBM tumors and not expressed, or very infrequently and at low levels, in healthy tissues (including brain). These peptide-coding, GBM-specific, highly recurrent TEs represent potential tumor-specific targets for cancer immunotherapies.
我们使用一种整合了单细胞转录组学、肿瘤和健康组织队列的批量 RNA 测序（RNA-seq）样本以及免疫肽组学样本的蛋白质基因组学管道来分析胶质母细胞瘤（GBM）患者中的转座元件（TEs）。我们由此鉴定出 370 种在 GBM 中差异表达的由人类白细胞抗原（HLA）-I 结合的 TEs 编码的肽段。其中一些肽段由完整开放阅读框（ORF）中的重复序列编码，这些 ORF 存在于多达数百个来自近期长散布核元件（LINE）-1、长末端重复（LTR）和 SVA 亚家族的 TEs 中。其他由旧亚家族的单个 TEs 编码的 HLA-I 结合肽段在 GBM 肿瘤中反复表达，但在健康组织（包括大脑）中不表达或很少表达且水平很低。这些编码肽段、在 GBM 中特异性高且反复出现的 TEs 代表癌症免疫疗法的潜在肿瘤特异性靶标。
