Using single-cell and bulk transcriptomic samples and immunopeptidomic datasets, Bonté and Arribas et al. identified HLA-I-bound peptides encoded by transposable elements (TEs) that were differentially expressed in glioblastoma (GBM) and were immunogenic in vitro. Most peptides were encoded by repeat sequences from intact ORFs that were redundant across several hundred younger TEs, while some were encoded by single copies of TEs from old subfamilies. The latter were more likely to be recurrently and differentially expressed in GBM, and could serve as strong targets for immunotherapy.
Contributed by Lauren Hitchings
ABSTRACT: 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.
Author Info: (1) Institut Curie, PSL University, INSERM U932, Immunity and Cancer, 75005 Paris, France. (2) Institut Curie, PSL University, INSERM U932, Immunity and Cancer, 75005 Paris, France
Author Info: (1) Institut Curie, PSL University, INSERM U932, Immunity and Cancer, 75005 Paris, France. (2) Institut Curie, PSL University, INSERM U932, Immunity and Cancer, 75005 Paris, France. (3) Institut Curie, PSL University, INSERM U932, Immunity and Cancer, 75005 Paris, France. (4) Biological and Environmental Proteomics, Institut d'Investigacions Biomdiques de Barcelona-CSIC, IDIBAPS, Rosell 161, 6a planta, 08036 Barcelona, Spain. (5) GBM Translational Center of Excellence, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. (6) Institut Curie, PSL University, INSERM U932, Immunity and Cancer, 75005 Paris, France. (7) GBM Translational Center of Excellence, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. (8) 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. (9) Institut Curie, PSL University, INSERM U932, Immunity and Cancer, 75005 Paris, France. Electronic address: christel.goudot@curie.fr. (10) Institut Curie, PSL University, INSERM U932, Immunity and Cancer, 75005 Paris, France. Electronic address: sebastian.amigorena@curie.fr.
