PMID- 35675780 OWN - NLM STAT- MEDLINE DCOM- 20220610 LR - 20220912 IS - 2211-1247 (Electronic) VI - 39 IP - 10 DP - 2022 Jun 7 TI - Single-cell RNA-seq-based proteogenomics identifies glioblastoma-specific transposable elements encoding HLA-I-presented peptides. PG - 110916 LID - S2211-1247(22)00693-3 [pii] LID - 10.1016/j.celrep.2022.110916 [doi] AB - 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. CI - Copyright (c) 2022 Institut Curie. Published by Elsevier Inc. All rights reserved. FAU - Bonte, Pierre-Emmanuel AU - Bonte PE AD - Institut Curie, PSL University, INSERM U932, Immunity and Cancer, 75005 Paris, France. FAU - Arribas, Yago A AU - Arribas YA AD - Institut Curie, PSL University, INSERM U932, Immunity and Cancer, 75005 Paris, France. FAU - Merlotti, Antonela AU - Merlotti A AD - Institut Curie, PSL University, INSERM U932, Immunity and Cancer, 75005 Paris, France. FAU - Carrascal, Montserrat AU - Carrascal M AD - Biological and Environmental Proteomics, Institut d'Investigacions Biomediques de Barcelona-CSIC, IDIBAPS, Rosello 161, 6a planta, 08036 Barcelona, Spain. FAU - Zhang, Jiasi Vicky AU - Zhang JV AD - GBM Translational Center of Excellence, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. FAU - Zueva, Elina AU - Zueva E AD - Institut Curie, PSL University, INSERM U932, Immunity and Cancer, 75005 Paris, France. FAU - Binder, Zev A AU - Binder ZA AD - GBM Translational Center of Excellence, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. FAU - Alanio, Cecile AU - Alanio C AD - Institut Curie, PSL University, INSERM U932, Immunity and Cancer, 75005 Paris, France; Laboratoire d'Immunologie Clinique, Institut Curie, Paris 75005, France; Parker Institute of Cancer Immunotherapy, San Francisco, CA, USA. FAU - Goudot, Christel AU - Goudot C AD - Institut Curie, PSL University, INSERM U932, Immunity and Cancer, 75005 Paris, France. Electronic address: christel.goudot@curie.fr. FAU - Amigorena, Sebastian AU - Amigorena S AD - Institut Curie, PSL University, INSERM U932, Immunity and Cancer, 75005 Paris, France. Electronic address: sebastian.amigorena@curie.fr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Cell Rep JT - Cell reports JID - 101573691 RN - 0 (DNA Transposable Elements) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Peptides) SB - IM MH - DNA Transposable Elements MH - *Glioblastoma/genetics MH - *Histocompatibility Antigens Class I/genetics MH - Humans MH - Peptides/genetics MH - *Proteogenomics MH - RNA-Seq OTO - NOTNLM OT - HLA-I OT - cancer immunotherapy OT - endogenous retrovirus OT - glioblastoma OT - immunopeptidomics OT - neoantigen OT - non-canonical proteome OT - non-coding genome OT - single-cell RNA-seq OT - transposable elements COIS- Declaration of interests C.A. is a consultant for Biotherapy Partners. S.A. is shareholder and consultant for Mnemo Therapeutics. P.-E.B., Y.A.A., A.M., E.Z., and C.G. are consultants for Mnemo Therapeutics. A patent related to this work has been deposited under number EP22305355 in European Patent Application. EDAT- 2022/06/09 06:00 MHDA- 2022/06/11 06:00 CRDT- 2022/06/08 18:23 PHST- 2021/09/21 00:00 [received] PHST- 2022/03/22 00:00 [revised] PHST- 2022/05/12 00:00 [accepted] PHST- 2022/06/08 18:23 [entrez] PHST- 2022/06/09 06:00 [pubmed] PHST- 2022/06/11 06:00 [medline] AID - S2211-1247(22)00693-3 [pii] AID - 10.1016/j.celrep.2022.110916 [doi] PST - ppublish SO - Cell Rep. 2022 Jun 7;39(10):110916. doi: 10.1016/j.celrep.2022.110916.