PMID- 37978195
OWN - NLM
STAT- MEDLINE
DCOM- 20231127
LR  - 20231127
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 14
IP  - 1
DP  - 2023 Nov 17
TI  - TOF(IMS) mass spectrometry-based immunopeptidomics refines tumor antigen 
      identification.
PG  - 7472
LID - 10.1038/s41467-023-42692-7 [doi]
LID - 7472
AB  - T cell recognition of human leukocyte antigen (HLA)-presented tumor-associated 
      peptides is central for cancer immune surveillance. Mass spectrometry (MS)-based 
      immunopeptidomics represents the only unbiased method for the direct 
      identification and characterization of naturally presented tumor-associated 
      peptides, a key prerequisite for the development of T cell-based immunotherapies. 
      This study reports on the implementation of ion mobility separation-based 
      time-of-flight (TOF(IMS)) MS for next-generation immunopeptidomics, enabling 
      high-speed and sensitive detection of HLA-presented peptides. Applying 
      TOF(IMS)-based immunopeptidomics, a novel extensive benign(TOFIMS) dataset was 
      generated from 94 primary benign samples of solid tissue and hematological 
      origin, which enabled the expansion of benign reference immunopeptidome databases 
      with > 150,000 HLA-presented peptides, the refinement of previously described 
      tumor antigens, as well as the identification of frequently presented self 
      antigens and not yet described tumor antigens comprising low abundant 
      mutation-derived neoepitopes that might serve as targets for future cancer 
      immunotherapy development.
CI  - (c) 2023. The Author(s).
FAU - Hoenisch Gravel, Naomi
AU  - Hoenisch Gravel N
AUID- ORCID: 0000-0001-9465-0175
AD  - Department of Peptide-based Immunotherapy, University 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 - Nelde, Annika
AU  - Nelde A
AUID- ORCID: 0000-0001-8504-8481
AD  - Department of Peptide-based Immunotherapy, University 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 - Bauer, Jens
AU  - Bauer J
AUID- ORCID: 0000-0003-3731-2385
AD  - Department of Peptide-based Immunotherapy, University 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 - Muhlenbruch, Lena
AU  - Muhlenbruch L
AD  - Department of Peptide-based Immunotherapy, University 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  - German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), partner 
      site Tubingen, Tubingen, Germany.
FAU - Schroeder, Sarah M
AU  - Schroeder SM
AUID- ORCID: 0000-0002-4271-1498
AD  - Department of Peptide-based Immunotherapy, University and University Hospital 
      Tubingen, Tubingen, Germany.
AD  - Institute for Cell Biology, Department of Immunology, University of Tubingen, 
      Tubingen, Germany.
AD  - Department of Otorhinolaryngology, Head and Neck Surgery, University of Tubingen, 
      Tubingen, Germany.
FAU - Neidert, Marian C
AU  - Neidert MC
AD  - Neuroscience Center Zurich (ZNZ), University of Zurich and ETH Zurich, Zurich, 
      Switzerland.
AD  - Clinical Neuroscience Center and Department of Neurosurgery, University Hospital 
      and University of Zurich, Zurich, Switzerland.
AD  - Department of Neurosurgery, Cantonal Hospital St. Gallen, Zurich, Switzerland.
FAU - Scheid, Jonas
AU  - Scheid J
AUID- ORCID: 0000-0002-5923-1343
AD  - Department of Peptide-based Immunotherapy, University 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 - Lemke, Steffen
AU  - Lemke S
AD  - Department of Peptide-based Immunotherapy, University 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 L
AU  - Dubbelaar ML
AUID- ORCID: 0000-0002-4930-1467
AD  - Department of Peptide-based Immunotherapy, University 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 - Wacker, Marcel
AU  - Wacker M
AUID- ORCID: 0000-0002-8185-140X
AD  - Department of Peptide-based Immunotherapy, University 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 - Dengler, Anna
AU  - Dengler A
AD  - Department of Peptide-based Immunotherapy, University 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 - Klein, Reinhild
AU  - Klein R
AUID- ORCID: 0000-0002-6111-3901
AD  - Department of Hematology, Oncology, Clinical Immunology and Rheumatology, 
      University Hospital Tubingen, Tubingen, Germany.
FAU - Mauz, Paul-Stefan
AU  - Mauz PS
AD  - Department of Otorhinolaryngology, Head and Neck Surgery, University of Tubingen, 
      Tubingen, Germany.
FAU - Lowenheim, Hubert
AU  - Lowenheim H
AD  - Department of Otorhinolaryngology, Head and Neck Surgery, University of Tubingen, 
      Tubingen, Germany.
FAU - Hauri-Hohl, Mathias
AU  - Hauri-Hohl M
AD  - Pediatric Stem Cell Transplantation, University Children's Hospital Zurich, 
      Zurich, Switzerland.
FAU - Martin, Roland
AU  - Martin R
AUID- ORCID: 0000-0002-0982-1329
AD  - Neuroimmunology and MS Research, Neurology Clinic, University and University 
      Hospital Zurich, Zurich, Switzerland.
FAU - Hennenlotter, Jorg
AU  - Hennenlotter J
AUID- ORCID: 0000-0003-3827-6996
AD  - Department of Urology, University Hospital Tubingen, Tubingen, Germany.
FAU - Stenzl, Arnulf
AU  - Stenzl A
AD  - Department of Urology, University Hospital Tubingen, Tubingen, Germany.
FAU - Heitmann, Jonas S
AU  - Heitmann JS
AUID- ORCID: 0000-0002-7305-8620
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 - Salih, Helmut R
AU  - Salih HR
AUID- ORCID: 0000-0002-6719-1847
AD  - Cluster of Excellence iFIT (EXC2180) "Image-Guided and Functionally Instructed 
      Tumor Therapies", University of Tubingen, Tubingen, Germany.
AD  - German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), partner 
      site Tubingen, Tubingen, Germany.
AD  - Clinical Collaboration Unit Translational Immunology, German Cancer Consortium 
      (DKTK), Department of Internal Medicine, University Hospital Tubingen, Tubingen, 
      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) and German Cancer Research Center (DKFZ), partner 
      site Tubingen, Tubingen, Germany.
FAU - Walz, Juliane S
AU  - Walz JS
AUID- ORCID: 0000-0001-6404-7391
AD  - Department of Peptide-based Immunotherapy, University 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.
LA  - eng
PT  - Journal Article
DEP - 20231117
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (HLA Antigens)
RN  - 0 (Peptides)
RN  - 0 (Histocompatibility Antigens Class II)
SB  - IM
MH  - Humans
MH  - *Histocompatibility Antigens Class I
MH  - Antigens, Neoplasm
MH  - Mass Spectrometry/methods
MH  - HLA Antigens
MH  - *Neoplasms/therapy
MH  - Peptides/chemistry
MH  - Histocompatibility Antigens Class II
PMC - PMC10656517
COIS- The authors declare no competing interests.
EDAT- 2023/11/18 11:44
MHDA- 2023/11/27 12:42
PMCR- 2023/11/17
CRDT- 2023/11/18 00:02
PHST- 2023/01/12 00:00 [received]
PHST- 2023/10/18 00:00 [accepted]
PHST- 2023/11/27 12:42 [medline]
PHST- 2023/11/18 11:44 [pubmed]
PHST- 2023/11/18 00:02 [entrez]
PHST- 2023/11/17 00:00 [pmc-release]
AID - 10.1038/s41467-023-42692-7 [pii]
AID - 42692 [pii]
AID - 10.1038/s41467-023-42692-7 [doi]
PST - epublish
SO  - Nat Commun. 2023 Nov 17;14(1):7472. doi: 10.1038/s41467-023-42692-7.