PMID- 37872136
OWN - NLM
STAT- MEDLINE
DCOM- 20231027
LR  - 20231119
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 14
IP  - 1
DP  - 2023 Oct 23
TI  - DNMT and HDAC inhibition induces immunogenic neoantigens from human endogenous 
      retroviral element-derived transcripts.
PG  - 6731
LID - 10.1038/s41467-023-42417-w [doi]
LID - 6731
AB  - Immunotherapies targeting cancer-specific neoantigens have revolutionized the 
      treatment of cancer patients. Recent evidence suggests that epigenetic therapies 
      synergize with immunotherapies, mediated by the de-repression of endogenous 
      retroviral element (ERV)-encoded promoters, and the initiation of transcription. 
      Here, we use deep RNA sequencing from cancer cell lines treated with DNA 
      methyltransferase inhibitor (DNMTi) and/or Histone deacetylase inhibitor (HDACi), 
      to assemble a de novo transcriptome and identify several thousand ERV-derived, 
      treatment-induced novel polyadenylated transcripts (TINPATs). Using 
      immunopeptidomics, we demonstrate the human leukocyte antigen (HLA) presentation 
      of 45 spectra-validated treatment-induced neopeptides (t-neopeptides) arising 
      from TINPATs. We illustrate the potential of the identified t-neopeptides to 
      elicit a T-cell response to effectively target cancer cells. We further verify 
      the presence of t-neopeptides in AML patient samples after in vivo treatment with 
      the DNMT inhibitor Decitabine. Our findings highlight the potential of 
      ERV-derived neoantigens in epigenetic and immune therapies.
CI  - (c) 2023. Springer Nature Limited.
FAU - Goyal, Ashish
AU  - Goyal A
AD  - Cancer Epigenomics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
FAU - Bauer, Jens
AU  - Bauer J
AUID- ORCID: 0000-0003-3731-2385
AD  - Department of Peptide-based Immunotherapy, University of Tubingen and University 
      Hospital Tubingen, Tubingen, Germany.
AD  - Institute for Cell Biology, Department of Immunology, University of Tubingen, 
      Tubingen, Germany.
AD  - Cluster of Excellence iFIT (EXC2180) "Image-Guided and Functionally Instructed 
      Tumor Therapies", University of Tubingen, Tubingen, Germany.
FAU - Hey, Joschka
AU  - Hey J
AUID- ORCID: 0000-0003-2842-764X
AD  - Cancer Epigenomics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
AD  - German-Israeli Helmholtz Research School in Cancer Biology, Heidelberg, Germany.
AD  - German Center for Lung Research, (DZL) partner site Heidelberg, Heidelberg, 
      Germany.
FAU - Papageorgiou, Dimitris N
AU  - Papageorgiou DN
AD  - Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center 
      (DKFZ), Heidelberg, Germany.
AD  - Heidelberg University, Medical Faculty, Heidelberg, Germany.
FAU - Stepanova, Ekaterina
AU  - Stepanova E
AD  - Translational Control and Metabolism, German Cancer Research Center (DKFZ), 
      Heidelberg, Germany.
FAU - Daskalakis, Michael
AU  - Daskalakis M
AUID- ORCID: 0000-0002-8138-0505
AD  - Cancer Epigenomics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
AD  - Department of Hematology and Central Hematology Laboratory, Inselspital, Bern, 
      University Hospital, University of Bern, Bern, Switzerland.
FAU - Scheid, Jonas
AU  - Scheid J
AUID- ORCID: 0000-0002-5923-1343
AD  - Department of Peptide-based Immunotherapy, University of Tubingen and University 
      Hospital Tubingen, Tubingen, Germany.
AD  - Institute for Cell Biology, Department of Immunology, University of Tubingen, 
      Tubingen, Germany.
AD  - Cluster of Excellence iFIT (EXC2180) "Image-Guided and Functionally Instructed 
      Tumor Therapies", University of Tubingen, Tubingen, Germany.
AD  - Quantitative Biology Center (QBiC), University of Tubingen, Tubingen, Germany.
FAU - Dubbelaar, Marissa
AU  - Dubbelaar M
AUID- ORCID: 0000-0002-4930-1467
AD  - Department of Peptide-based Immunotherapy, University of Tubingen and University 
      Hospital Tubingen, Tubingen, Germany.
AD  - Institute for Cell Biology, Department of Immunology, University of Tubingen, 
      Tubingen, Germany.
AD  - Cluster of Excellence iFIT (EXC2180) "Image-Guided and Functionally Instructed 
      Tumor Therapies", University of Tubingen, Tubingen, Germany.
AD  - Quantitative Biology Center (QBiC), University of Tubingen, Tubingen, Germany.
FAU - Klimovich, Boris
AU  - Klimovich B
AD  - Cluster of Excellence iFIT (EXC2180) "Image-Guided and Functionally Instructed 
      Tumor Therapies", University of Tubingen, Tubingen, Germany.
AD  - Clinical Collaboration Unit Translational Immunology, German Cancer Consortium 
      (DKTK), Department of Internal Medicine, University Hospital Tubingen, Tubingen, 
      Germany.
FAU - Schwarz, Dominic
AU  - Schwarz D
AUID- ORCID: 0000-0001-7260-2033
AD  - Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center 
      (DKFZ), Heidelberg, Germany.
FAU - Marklin, Melanie
AU  - Marklin M
AUID- ORCID: 0000-0002-2920-3894
AD  - Cluster of Excellence iFIT (EXC2180) "Image-Guided and Functionally Instructed 
      Tumor Therapies", University of Tubingen, Tubingen, Germany.
AD  - Clinical Collaboration Unit Translational Immunology, German Cancer Consortium 
      (DKTK), Department of Internal Medicine, University Hospital Tubingen, Tubingen, 
      Germany.
FAU - Roerden, Malte
AU  - Roerden M
AD  - Department of Peptide-based Immunotherapy, University of Tubingen and University 
      Hospital Tubingen, Tubingen, Germany.
AD  - Cluster of Excellence iFIT (EXC2180) "Image-Guided and Functionally Instructed 
      Tumor Therapies", University of Tubingen, Tubingen, Germany.
FAU - Lin, Yu-Yu
AU  - Lin YY
AD  - Cancer Epigenomics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
FAU - Ma, Tobias
AU  - Ma T
AUID- ORCID: 0009-0009-1258-8976
AD  - Department of Hematology, Oncology and Stem Cell Transplantation, University 
      Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, 
      Germany.
FAU - Mucke, Oliver
AU  - Mucke O
AD  - Cancer Epigenomics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
FAU - Rammensee, Hans-Georg
AU  - Rammensee HG
AD  - Institute for Cell Biology, Department of Immunology, University of Tubingen, 
      Tubingen, Germany.
AD  - Cluster of Excellence iFIT (EXC2180) "Image-Guided and Functionally Instructed 
      Tumor Therapies", University of Tubingen, Tubingen, Germany.
AD  - German Cancer Consortium (DKTK), Heidelberg, Germany.
FAU - Lubbert, Michael
AU  - Lubbert M
AUID- ORCID: 0000-0003-1186-1650
AD  - Department of Hematology, Oncology and Stem Cell Transplantation, University 
      Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, 
      Germany.
FAU - Loayza-Puch, Fabricio
AU  - Loayza-Puch F
AUID- ORCID: 0000-0002-2999-8594
AD  - Translational Control and Metabolism, German Cancer Research Center (DKFZ), 
      Heidelberg, Germany.
FAU - Krijgsveld, Jeroen
AU  - Krijgsveld J
AUID- ORCID: 0000-0001-7549-9326
AD  - Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center 
      (DKFZ), Heidelberg, Germany.
AD  - Heidelberg University, Medical Faculty, Heidelberg, Germany.
FAU - Walz, Juliane S
AU  - Walz JS
AUID- ORCID: 0000-0001-6404-7391
AD  - Department of Peptide-based Immunotherapy, University of Tubingen and University 
      Hospital Tubingen, Tubingen, Germany. juliane.walz@med.uni-tuebingen.de.
AD  - Institute for Cell Biology, Department of Immunology, University of Tubingen, 
      Tubingen, Germany. juliane.walz@med.uni-tuebingen.de.
AD  - Cluster of Excellence iFIT (EXC2180) "Image-Guided and Functionally Instructed 
      Tumor Therapies", University of Tubingen, Tubingen, Germany. 
      juliane.walz@med.uni-tuebingen.de.
AD  - Clinical Collaboration Unit Translational Immunology, German Cancer Consortium 
      (DKTK), Department of Internal Medicine, University Hospital Tubingen, Tubingen, 
      Germany. juliane.walz@med.uni-tuebingen.de.
FAU - Plass, Christoph
AU  - Plass C
AUID- ORCID: 0000-0003-2554-3952
AD  - Cancer Epigenomics, German Cancer Research Center (DKFZ), Heidelberg, Germany. 
      c.plass@dkfz.de.
AD  - German Center for Lung Research, (DZL) partner site Heidelberg, Heidelberg, 
      Germany. c.plass@dkfz.de.
AD  - German Cancer Consortium (DKTK), Heidelberg, Germany. c.plass@dkfz.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20231023
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Histocompatibility Antigens Class I)
SB  - IM
MH  - Humans
MH  - *Endogenous Retroviruses/genetics
MH  - Histone Deacetylase Inhibitors/pharmacology
MH  - *Neoplasms
MH  - T-Lymphocytes
MH  - Histocompatibility Antigens Class I
PMC - PMC10593957
COIS- The University Hospital Tubingen and German Cancer Research Center (DKFZ, 
      Heidelberg) is in the process of applying for a patent application (Patent 
      number: EP23170469.3, Title: Neoepitope immunogenic peptides for cancer treatment 
      and diagnosis) covering t-neopeptides that lists A.G., J.B., J.H., J.S.W, and 
      C.P. as inventors. The other authors declare no competing interests.
EDAT- 2023/10/24 00:41
MHDA- 2023/10/27 06:42
PMCR- 2023/10/23
CRDT- 2023/10/23 23:16
PHST- 2022/10/04 00:00 [received]
PHST- 2023/10/11 00:00 [accepted]
PHST- 2023/10/27 06:42 [medline]
PHST- 2023/10/24 00:41 [pubmed]
PHST- 2023/10/23 23:16 [entrez]
PHST- 2023/10/23 00:00 [pmc-release]
AID - 10.1038/s41467-023-42417-w [pii]
AID - 42417 [pii]
AID - 10.1038/s41467-023-42417-w [doi]
PST - epublish
SO  - Nat Commun. 2023 Oct 23;14(1):6731. doi: 10.1038/s41467-023-42417-w.