PMID- 33087703
OWN - NLM
STAT- MEDLINE
DCOM- 20201109
LR  - 20211204
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 11
IP  - 1
DP  - 2020 Oct 21
TI  - Single-cell derived tumor organoids display diversity in HLA class I peptide 
      presentation.
PG  - 5338
LID - 10.1038/s41467-020-19142-9 [doi]
LID - 5338
AB  - Tumor heterogeneity is a major cause of therapeutic resistance. Immunotherapy may 
      exploit alternative vulnerabilities of drug-resistant cells, where tumor-specific 
      human leukocyte antigen (HLA) peptide ligands are promising leads to invoke 
      targeted anti-tumor responses. Here, we investigate the variability in HLA class 
      I peptide presentation between different clonal cells of the same colorectal 
      cancer patient, using an organoid system. While clone-specific differences in HLA 
      peptide presentation were observed, broad inter-clone variability was even more 
      prevalent (15-25%). By coupling organoid proteomics and HLA peptide ligandomics, 
      we also found that tumor-specific ligands from DNA damage control and tumor 
      suppressor source proteins were prominently presented by tumor cells, coinciding 
      likely with the silencing of such cytoprotective functions. Collectively, these 
      data illustrate the heterogeneous HLA peptide presentation landscape even within 
      one individual, and hint that a multi-peptide vaccination approach against highly 
      conserved tumor suppressors may be a viable option in patients with low 
      tumor-mutational burden.
FAU - Demmers, Laura C
AU  - Demmers LC
AD  - Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular 
      Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 
      Padualaan 8, 3584 CH, Utrecht, The Netherlands.
AD  - Netherlands Proteomics Centre, Padualaan 8, 3584 CH, Utrecht, The Netherlands.
FAU - Kretzschmar, Kai
AU  - Kretzschmar K
AUID- ORCID: 0000-0002-4745-6684
AD  - Oncode Institute, Hubrecht Institute, 3584 CT, Utrecht, The Netherlands.
AD  - Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University 
      Medical Centre Utrecht, 3584 CT, Utrecht, The Netherlands.
FAU - Van Hoeck, Arne
AU  - Van Hoeck A
AUID- ORCID: 0000-0002-6570-1452
AD  - Center for Molecular Medicine and Oncode Institute, University Medical Center 
      Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands.
FAU - Bar-Epraim, Yotam E
AU  - Bar-Epraim YE
AD  - Oncode Institute, Hubrecht Institute, 3584 CT, Utrecht, The Netherlands.
AD  - Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University 
      Medical Centre Utrecht, 3584 CT, Utrecht, The Netherlands.
FAU - van den Toorn, Henk W P
AU  - van den Toorn HWP
AUID- ORCID: 0000-0002-0270-5763
AD  - Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular 
      Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 
      Padualaan 8, 3584 CH, Utrecht, The Netherlands.
AD  - Netherlands Proteomics Centre, Padualaan 8, 3584 CH, Utrecht, The Netherlands.
FAU - Koomen, Mandy
AU  - Koomen M
AD  - Oncode Institute, Hubrecht Institute, 3584 CT, Utrecht, The Netherlands.
AD  - Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University 
      Medical Centre Utrecht, 3584 CT, Utrecht, The Netherlands.
FAU - van Son, Gijs
AU  - van Son G
AD  - Oncode Institute, Hubrecht Institute, 3584 CT, Utrecht, The Netherlands.
AD  - Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University 
      Medical Centre Utrecht, 3584 CT, Utrecht, The Netherlands.
FAU - van Gorp, Joost
AU  - van Gorp J
AD  - Department of Pathology, St. Antonius Hospital, 3543 AZ, Utrecht, The 
      Netherlands.
FAU - Pronk, Apollo
AU  - Pronk A
AD  - Department of Surgery, Diakonessenhuis Hospital, 3582 KE, Utrecht, The 
      Netherlands.
FAU - Smakman, Niels
AU  - Smakman N
AD  - Department of Surgery, Diakonessenhuis Hospital, 3582 KE, Utrecht, The 
      Netherlands.
FAU - Cuppen, Edwin
AU  - Cuppen E
AD  - Center for Molecular Medicine and Oncode Institute, University Medical Center 
      Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands.
AD  - Hartwig Medical Foundation, 1098 XH, Amsterdam, The Netherlands.
FAU - Clevers, Hans
AU  - Clevers H
AUID- ORCID: 0000-0002-3077-5582
AD  - Oncode Institute, Hubrecht Institute, 3584 CT, Utrecht, The Netherlands.
AD  - Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University 
      Medical Centre Utrecht, 3584 CT, Utrecht, The Netherlands.
AD  - Princess Maxima Center for Pediatric Oncology, 3584 CS, Utrecht, The Netherlands.
FAU - Heck, Albert J R
AU  - Heck AJR
AUID- ORCID: 0000-0002-2405-4404
AD  - Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular 
      Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 
      Padualaan 8, 3584 CH, Utrecht, The Netherlands. a.j.r.heck@uu.nl.
AD  - Netherlands Proteomics Centre, Padualaan 8, 3584 CH, Utrecht, The Netherlands. 
      a.j.r.heck@uu.nl.
FAU - Wu, Wei
AU  - Wu W
AUID- ORCID: 0000-0002-1092-603X
AD  - Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular 
      Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 
      Padualaan 8, 3584 CH, Utrecht, The Netherlands. w.wu1@uu.nl.
AD  - Netherlands Proteomics Centre, Padualaan 8, 3584 CH, Utrecht, The Netherlands. 
      w.wu1@uu.nl.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201021
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (HLA Antigens)
RN  - 0 (Ligands)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proteome)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Antigen Presentation
MH  - Cell Line, Tumor
MH  - Clone Cells/immunology/metabolism/pathology
MH  - Colorectal Neoplasms/*immunology/metabolism/pathology
MH  - HLA Antigens/*metabolism
MH  - Humans
MH  - Ligands
MH  - Models, Biological
MH  - Neoplasm Proteins/metabolism
MH  - Organoids/*immunology/metabolism/pathology
MH  - Proteome/metabolism
MH  - Signal Transduction
MH  - Single-Cell Analysis
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC7577990
COIS- H.C., K.K., and Y.E.B.E. are named inventors on several patents or patent 
      applications related to organoid technology. All other authors declare no 
      competing interests.
EDAT- 2020/10/23 06:00
MHDA- 2020/11/11 06:00
PMCR- 2020/10/21
CRDT- 2020/10/22 05:30
PHST- 2020/01/16 00:00 [received]
PHST- 2020/10/02 00:00 [accepted]
PHST- 2020/10/22 05:30 [entrez]
PHST- 2020/10/23 06:00 [pubmed]
PHST- 2020/11/11 06:00 [medline]
PHST- 2020/10/21 00:00 [pmc-release]
AID - 10.1038/s41467-020-19142-9 [pii]
AID - 19142 [pii]
AID - 10.1038/s41467-020-19142-9 [doi]
PST - epublish
SO  - Nat Commun. 2020 Oct 21;11(1):5338. doi: 10.1038/s41467-020-19142-9.