PMID- 38490980
OWN - NLM
STAT- MEDLINE
DCOM- 20240318
LR  - 20240318
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 15
IP  - 1
DP  - 2024 Mar 15
TI  - Immunopeptidomics-based identification of naturally presented non-canonical 
      circRNA-derived peptides.
PG  - 2357
LID - 10.1038/s41467-024-46408-3 [doi]
LID - 2357
AB  - Circular RNAs (circRNAs) are covalently closed non-coding RNAs lacking the 5' cap 
      and the poly-A tail. Nevertheless, it has been demonstrated that certain circRNAs 
      can undergo active translation. Therefore, aberrantly expressed circRNAs in human 
      cancers could be an unexplored source of tumor-specific antigens, potentially 
      mediating anti-tumor T cell responses. This study presents an immunopeptidomics 
      workflow with a specific focus on generating a circRNA-specific protein fasta 
      reference. The main goal of this workflow is to streamline the process of 
      identifying and validating human leukocyte antigen (HLA) bound peptides 
      potentially originating from circRNAs. We increase the analytical stringency of 
      our workflow by retaining peptides identified independently by two mass 
      spectrometry search engines and/or by applying a group-specific FDR for 
      canonical-derived and circRNA-derived peptides. A subset of circRNA-derived 
      peptides specifically encoded by the region spanning the back-splice junction 
      (BSJ) are validated with targeted MS, and with direct Sanger sequencing of the 
      respective source transcripts. Our workflow identifies 54 unique BSJ-spanning 
      circRNA-derived peptides in the immunopeptidome of melanoma and lung cancer 
      samples. Our approach enlarges the catalog of source proteins that can be 
      explored for immunotherapy.
CI  - (c) 2024. The Author(s).
FAU - Ferreira, Humberto J
AU  - Ferreira HJ
AUID- ORCID: 0000-0003-0834-2956
AD  - Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, 
      Switzerland.
AD  - Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, 
      Switzerland.
AD  - Agora Cancer Research Centre, Lausanne, Switzerland.
FAU - Stevenson, Brian J
AU  - Stevenson BJ
AD  - Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, 
      Switzerland.
AD  - Agora Cancer Research Centre, Lausanne, Switzerland.
AD  - SIB Swiss Institute of Bioinformatics, University of Lausanne, Lausanne, 
      Switzerland.
FAU - Pak, HuiSong
AU  - Pak H
AD  - Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, 
      Switzerland.
AD  - Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, 
      Switzerland.
AD  - Agora Cancer Research Centre, Lausanne, Switzerland.
FAU - Yu, Fengchao
AU  - Yu F
AUID- ORCID: 0000-0002-7695-3698
AD  - Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
FAU - Almeida Oliveira, Jessica
AU  - Almeida Oliveira J
AUID- ORCID: 0009-0004-4447-1872
AD  - Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, 
      Switzerland.
AD  - Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, 
      Switzerland.
AD  - Agora Cancer Research Centre, Lausanne, Switzerland.
FAU - Huber, Florian
AU  - Huber F
AUID- ORCID: 0000-0002-2585-9079
AD  - Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, 
      Switzerland.
AD  - Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, 
      Switzerland.
AD  - Agora Cancer Research Centre, Lausanne, Switzerland.
FAU - Taillandier-Coindard, Marie
AU  - Taillandier-Coindard M
AD  - Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, 
      Switzerland.
AD  - Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, 
      Switzerland.
AD  - Agora Cancer Research Centre, Lausanne, Switzerland.
FAU - Michaux, Justine
AU  - Michaux J
AD  - Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, 
      Switzerland.
AD  - Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, 
      Switzerland.
AD  - Agora Cancer Research Centre, Lausanne, Switzerland.
FAU - Ricart-Altimiras, Emma
AU  - Ricart-Altimiras E
AD  - Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, 
      Switzerland.
AD  - Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, 
      Switzerland.
AD  - Agora Cancer Research Centre, Lausanne, Switzerland.
FAU - Kraemer, Anne I
AU  - Kraemer AI
AD  - Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, 
      Switzerland.
AD  - Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, 
      Switzerland.
AD  - Agora Cancer Research Centre, Lausanne, Switzerland.
FAU - Kandalaft, Lana E
AU  - Kandalaft LE
AUID- ORCID: 0000-0002-1575-6674
AD  - Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, 
      Switzerland.
AD  - Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, 
      Switzerland.
AD  - Agora Cancer Research Centre, Lausanne, Switzerland.
AD  - Center of Experimental Therapeutics, Department of Oncology, Centre Hospitalier 
      Universitaire Vaudois, Lausanne, Switzerland.
FAU - Speiser, Daniel E
AU  - Speiser DE
AUID- ORCID: 0000-0003-2031-3250
AD  - Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, 
      Switzerland.
FAU - Nesvizhskii, Alexey I
AU  - Nesvizhskii AI
AUID- ORCID: 0000-0002-2806-7819
AD  - Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
AD  - Department of Computational Medicine and Bioinformatics, University of Michigan, 
      Ann Arbor, MI, USA.
FAU - Muller, Markus
AU  - Muller M
AUID- ORCID: 0000-0003-0907-3583
AD  - Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, 
      Switzerland.
AD  - Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, 
      Switzerland.
AD  - Agora Cancer Research Centre, Lausanne, Switzerland.
AD  - SIB Swiss Institute of Bioinformatics, University of Lausanne, Lausanne, 
      Switzerland.
FAU - Bassani-Sternberg, Michal
AU  - Bassani-Sternberg M
AUID- ORCID: 0000-0002-1934-954X
AD  - Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, 
      Switzerland. michal.bassani@chuv.ch.
AD  - Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, 
      Switzerland. michal.bassani@chuv.ch.
AD  - Agora Cancer Research Centre, Lausanne, Switzerland. michal.bassani@chuv.ch.
AD  - Center of Experimental Therapeutics, Department of Oncology, Centre Hospitalier 
      Universitaire Vaudois, Lausanne, Switzerland. michal.bassani@chuv.ch.
LA  - eng
PT  - Journal Article
DEP - 20240315
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (RNA, Circular)
RN  - 0 (RNA, Messenger)
RN  - 0 (Peptides)
RN  - 0 (Histocompatibility Antigens Class I)
SB  - IM
MH  - Humans
MH  - *RNA, Circular/metabolism
MH  - RNA, Messenger
MH  - *Peptides
MH  - Histocompatibility Antigens Class I
PMC - PMC10943130
COIS- The authors declare no competing interests.
EDAT- 2024/03/16 21:42
MHDA- 2024/03/18 06:43
PMCR- 2024/03/15
CRDT- 2024/03/16 00:13
PHST- 2023/07/21 00:00 [received]
PHST- 2024/02/16 00:00 [accepted]
PHST- 2024/03/18 06:43 [medline]
PHST- 2024/03/16 21:42 [pubmed]
PHST- 2024/03/16 00:13 [entrez]
PHST- 2024/03/15 00:00 [pmc-release]
AID - 10.1038/s41467-024-46408-3 [pii]
AID - 46408 [pii]
AID - 10.1038/s41467-024-46408-3 [doi]
PST - epublish
SO  - Nat Commun. 2024 Mar 15;15(1):2357. doi: 10.1038/s41467-024-46408-3.