Single-cell RNA-seq-based proteogenomics identifies glioblastoma-specific transposable elements encoding HLA-I-presented peptides.

DNA Transposable Elements Glioblastoma / genetics Histocompatibility Antigens Class I / genetics Humans Peptides / genetics Proteogenomics RNA-Seq
HLA-I cancer immunotherapy endogenous retrovirus glioblastoma immunopeptidomics neoantigen non-canonical proteome non-coding genome single-cell RNA-seq transposable elements

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
07 06 2022
Historique:
received: 21 09 2021
revised: 22 03 2022
accepted: 12 05 2022
entrez: 8 6 2022
pubmed: 9 6 2022
medline: 11 6 2022
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.celrep.2022.110916 PMID: 35675780
pubmed: 35675780
pii: S2211-1247(22)00693-3
doi: 10.1016/j.celrep.2022.110916
pii:
doi:

Substances chimiques

DNA Transposable Elements 0
Histocompatibility Antigens Class I 0
Peptides 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

110916

Informations de copyright

Copyright © 2022 Institut Curie. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

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.

Auteurs

Pierre-Emmanuel Bonté (PE)

Institut Curie, PSL University, INSERM U932, Immunity and Cancer, 75005 Paris, France.

Yago A Arribas (YA)

Institut Curie, PSL University, INSERM U932, Immunity and Cancer, 75005 Paris, France.

Antonela Merlotti (A)

Institut Curie, PSL University, INSERM U932, Immunity and Cancer, 75005 Paris, France.

Montserrat Carrascal (M)

Biological and Environmental Proteomics, Institut d'Investigacions Biomèdiques de Barcelona-CSIC, IDIBAPS, Roselló 161, 6a planta, 08036 Barcelona, Spain.

Jiasi Vicky Zhang (JV)

GBM Translational Center of Excellence, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Elina Zueva (E)

Institut Curie, PSL University, INSERM U932, Immunity and Cancer, 75005 Paris, France.

Zev A Binder (ZA)

GBM Translational Center of Excellence, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Cécile Alanio (C)

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.

Christel Goudot (C)

Institut Curie, PSL University, INSERM U932, Immunity and Cancer, 75005 Paris, France. Electronic address: christel.goudot@curie.fr.

Sebastian Amigorena (S)

Institut Curie, PSL University, INSERM U932, Immunity and Cancer, 75005 Paris, France. Electronic address: sebastian.amigorena@curie.fr.

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Classifications MeSH

questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Séquences répétées dispersées › Éléments transposables d'ADN › Single-cell RNA-seq-based proteogenomics...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs du tissu nerveux › Tumeurs neuroectodermiques › Tumeurs neuroépitheliales › Gliome › Astrocytome › Glioblastome › Single-cell RNA-seq-based proteogenomics...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Isoantigènes › Antigènes d'histocompatibilité › Antigènes d'histocompatibilité de classe I › Single-cell RNA-seq-based proteogenomics...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Single-cell RNA-seq-based proteogenomics...
questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Single-cell RNA-seq-based proteogenomics...
questionsmedicales.fr › Disciplines des sciences naturelles › Chimie › Biochimie › Protéomique › Protéogénomique › Single-cell RNA-seq-based proteogenomics...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ARN › RNA-Seq › Single-cell RNA-seq-based proteogenomics...