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Human endogenous retroviruses form a reservoir of T cell targets in hematological cancers

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Harvard

Saini, SK, Ørskov, AD, Bjerregaard, A-M, Unnikrishnan, A, Holmberg-Thydén, S, Borch, A, Jensen, KV, Anande, G, Bentzen, AK, Marquard, AM, Tamhane, T, Treppendahl, MB, Gang, AO, Dufva, IH, Szallasi, Z, Ternette, N, Pedersen, AG, Eklund, AC, Pimanda, J, Grønbæk, K & Hadrup, SR 2020, 'Human endogenous retroviruses form a reservoir of T cell targets in hematological cancers', Nature Communications, bind 11, nr. 1, 5660. https://doi.org/10.1038/s41467-020-19464-8

APA

Saini, S. K., Ørskov, A. D., Bjerregaard, A-M., Unnikrishnan, A., Holmberg-Thydén, S., Borch, A., Jensen, K. V., Anande, G., Bentzen, A. K., Marquard, A. M., Tamhane, T., Treppendahl, M. B., Gang, A. O., Dufva, I. H., Szallasi, Z., Ternette, N., Pedersen, A. G., Eklund, A. C., Pimanda, J., ... Hadrup, S. R. (2020). Human endogenous retroviruses form a reservoir of T cell targets in hematological cancers. Nature Communications, 11(1), [5660]. https://doi.org/10.1038/s41467-020-19464-8

CBE

Saini SK, Ørskov AD, Bjerregaard A-M, Unnikrishnan A, Holmberg-Thydén S, Borch A, Jensen KV, Anande G, Bentzen AK, Marquard AM, Tamhane T, Treppendahl MB, Gang AO, Dufva IH, Szallasi Z, Ternette N, Pedersen AG, Eklund AC, Pimanda J, Grønbæk K, Hadrup SR. 2020. Human endogenous retroviruses form a reservoir of T cell targets in hematological cancers. Nature Communications. 11(1):Article 5660. https://doi.org/10.1038/s41467-020-19464-8

MLA

Vancouver

Author

Saini, Sunil Kumar ; Ørskov, Andreas Due ; Bjerregaard, Anne-Mette ; Unnikrishnan, Ashwin ; Holmberg-Thydén, Staffan ; Borch, Annie ; Jensen, Kathrine Valentini ; Anande, Govardhan ; Bentzen, Amalie Kai ; Marquard, Andrea Marion ; Tamhane, Tripti ; Treppendahl, Marianne Bach ; Gang, Anne Ortved ; Dufva, Inge Høgh ; Szallasi, Zoltan ; Ternette, Nicola ; Pedersen, Anders Gorm ; Eklund, Aron Charles ; Pimanda, John ; Grønbæk, Kirsten ; Hadrup, Sine Reker. / Human endogenous retroviruses form a reservoir of T cell targets in hematological cancers. I: Nature Communications. 2020 ; Bind 11, Nr. 1.

Bibtex

@article{23e3d9130d344dc194c46e771abe0a27,
title = "Human endogenous retroviruses form a reservoir of T cell targets in hematological cancers",
abstract = "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.",
keywords = "CD8-Positive T-Lymphocytes, Endogenous Retroviruses/genetics, Epigenesis, Genetic, Epitopes, T-Lymphocyte, Gene Expression Profiling, Hematologic Neoplasms/genetics, Humans, Immunotherapy, Monitoring, Immunologic, Myeloid Cells, Neoplasms, T-Lymphocytes/metabolism",
author = "Saini, {Sunil Kumar} and {\O}rskov, {Andreas Due} and Anne-Mette Bjerregaard and Ashwin Unnikrishnan and Staffan Holmberg-Thyd{\'e}n and Annie Borch and Jensen, {Kathrine Valentini} and Govardhan Anande and Bentzen, {Amalie Kai} and Marquard, {Andrea Marion} and Tripti Tamhane and Treppendahl, {Marianne Bach} and Gang, {Anne Ortved} and Dufva, {Inge H{\o}gh} and Zoltan Szallasi and Nicola Ternette and Pedersen, {Anders Gorm} and Eklund, {Aron Charles} and John Pimanda and Kirsten Gr{\o}nb{\ae}k and Hadrup, {Sine Reker}",
year = "2020",
month = nov,
day = "9",
doi = "10.1038/s41467-020-19464-8",
language = "English",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Human endogenous retroviruses form a reservoir of T cell targets in hematological cancers

AU - Saini, Sunil Kumar

AU - Ørskov, Andreas Due

AU - Bjerregaard, Anne-Mette

AU - Unnikrishnan, Ashwin

AU - Holmberg-Thydén, Staffan

AU - Borch, Annie

AU - Jensen, Kathrine Valentini

AU - Anande, Govardhan

AU - Bentzen, Amalie Kai

AU - Marquard, Andrea Marion

AU - Tamhane, Tripti

AU - Treppendahl, Marianne Bach

AU - Gang, Anne Ortved

AU - Dufva, Inge Høgh

AU - Szallasi, Zoltan

AU - Ternette, Nicola

AU - Pedersen, Anders Gorm

AU - Eklund, Aron Charles

AU - Pimanda, John

AU - Grønbæk, Kirsten

AU - Hadrup, Sine Reker

PY - 2020/11/9

Y1 - 2020/11/9

N2 - 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.

AB - 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.

KW - CD8-Positive T-Lymphocytes

KW - Endogenous Retroviruses/genetics

KW - Epigenesis, Genetic

KW - Epitopes, T-Lymphocyte

KW - Gene Expression Profiling

KW - Hematologic Neoplasms/genetics

KW - Humans

KW - Immunotherapy

KW - Monitoring, Immunologic

KW - Myeloid Cells

KW - Neoplasms

KW - T-Lymphocytes/metabolism

U2 - 10.1038/s41467-020-19464-8

DO - 10.1038/s41467-020-19464-8

M3 - Journal article

C2 - 33168830

VL - 11

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 5660

ER -

ID: 62022715