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

Pierre-Emmanuel Bonté (1) , Yago Arribas (1) , Antonela Merlotti (1) , Montserrat Carrascal (2) , Jiasi Vicky Zhang (3) , Elina Zueva (4, 1) , Zev Binder (3) , Cécile Alanio (1) , Christel Goudot (4, 1) , Sebastian Amigorena (4, 1)

1 U932 - Immunité et cancer
2 IIBB - Instituto de Investigaciones Biomedicas de Barcelona
3 Perelman School of Medicine
4 Institut Curie [Paris]

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.

Mots clés: HLA-I; cancer immunotherapy; endogenous retrovirus; glioblastoma; immunopeptidomics; neoantigen; non-canonical proteome; non-coding genome; single-cell RNA-seq; transposable elements

Domaines: Sciences du Vivant [q-bio]

Pierre-Emmanuel Bonté, Yago Arribas, Antonela Merlotti, Montserrat Carrascal, Jiasi Vicky Zhang, et al.. Single-cell RNA-seq-based proteogenomics identifies glioblastoma-specific transposable elements encoding HLA-I-presented peptides. Cell Reports, 2022, 39 (10), pp.110916. ⟨10.1016/j.celrep.2022.110916⟩. ⟨hal-03877461⟩