Journal article
Human endogenous retroviruses form a reservoir of T cell targets in hematological cancers
Department of Health Technology, Technical University of Denmark1
Experimental & Translational Immunology, Department of Health Technology, Technical University of Denmark2
T-Cells and Cancer, Experimental & Translational Immunology, Department of Health Technology, Technical University of Denmark3
University of Copenhagen4
University of New South Wales5
University of Oxford6
Human endogenous retroviruses (HERV) form a substantial part of the human genome, but mostly remain transcriptionally silent under strict epigenetic regulation, yet can potentially be reactivated by malignant transformation or epigenetic therapies. Here, we evaluate the potential for T cell recognition of HERV elements in myeloid malignancies by mapping transcribed HERV genes and generating a library of 1169 potential antigenic HERV-derived peptides predicted for presentation by 4 HLA class I molecules.
Using DNA barcode-labeled MHC-I multimers, we find CD8+ T cell populations recognizing 29 HERV-derived peptides representing 18 different HERV loci, of which HERVH-5, HERVW-1, and HERVE-3 have more profound responses; such HERV-specific T cells are present in 17 of the 34 patients, but less frequently in healthy donors.
Transcriptomic analyses reveal enhanced transcription of the HERVs in patients; meanwhile DNA-demethylating therapy causes a small and heterogeneous enhancement in HERV transcription without altering T cell recognition. Our study thus uncovers T cell recognition of HERVs in myeloid malignancies, thereby implicating HERVs as potential targets for immunotherapeutic therapies.
Language: | English |
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Publisher: | Nature Publishing Group UK |
Year: | 2020 |
Pages: | 5660 |
ISSN: | 20411723 |
Types: | Journal article |
DOI: | 10.1038/s41467-020-19464-8 |
ORCIDs: | 0000-0001-9996-7155 , 0000-0002-1831-6746 , 0000-0001-5168-8755 , 0000-0001-5357-0646 , 0000-0001-5395-7509 , 0000-0002-9283-0743 , Pedersen, Anders Gorm , 0000-0002-0509-8962 , Hadrup, Sine Reker , Saini, Sunil Kumar , Borch, Annie , Bentzen, Amalie Kai , Tamhane, Tripti and Eklund, Aron Charles |
CD8-Positive T-Lymphocytes Cancer immunotherapy Endogenous Retroviruses Epigenesis, Genetic Epitopes, T-Lymphocyte Gene Expression Profiling Hematologic Neoplasms Humans Immunosurveillance Immunotherapy MHC class I Monitoring, Immunologic Myeloid Cells Neoplasms Q Science T-Lymphocytes