PMID- 37503576
OWN - NLM
STAT- MEDLINE
DCOM- 20231023
LR  - 20231114
IS  - 1744-1358 (Electronic)
IS  - 0071-1365 (Linking)
VI  - 67
IP  - 6
DP  - 2023 Sep 28
TI  - What do cancer-specific CD8+ T cells see? The contribution of immunopeptidomics.
PG  - 957-965
LID - 10.1042/EBC20220246 [doi]
AB  - Immunopeptidomics is the survey of all peptides displayed on a cell or tissue 
      when bound to human leukocyte antigen (HLA) molecules using tandem mass 
      spectrometry. When attempting to determine the targets of tumour-specific CD8+ T 
      cells, a survey of the potential ligands in tumour tissues is invaluable, and, in 
      comparison with in-silico predictions, provides greater certainty of the 
      existence of individual epitopes, as immunopeptidomics-confirmed CD8+ T-cell 
      epitopes are known to be immunogenic, and direct observation should avoid the 
      risk of autoreactivity which could arise following immunisation with structural 
      homologues. The canonical sources of CD8+ T-cell tumour specific epitopes, such 
      as tumour associated antigens, may be well conserved between patients and tumour 
      types, but are often only weakly immunogenic. Direct observation of 
      tumour-specific neoantigens by immunopeptidomics is rare, although valuable. 
      Thus, there has been increasing interest in the non-canonical origins of 
      tumour-reactive CD8+ T-cell epitopes, such as those arising from proteasomal 
      splicing events, translational/turnover defects and alternative open reading 
      frame reads. Such epitopes can be identified in silico, although validation is 
      more challenging. Non-self CD8+ T-cell epitopes such as viral epitopes may be 
      useful in certain cancer types with known viral origins, however these have been 
      relatively unexplored with immunopeptidomics to date, possibly due to the paucity 
      of source viral proteins in tumour tissues. This review examines the latest 
      evidence for canonical, non-canonical and non-human CD8+ T-cell epitopes 
      identified by immunopeptidomics, and concludes that the relative contribution for 
      each of these sources to anti-tumour CD8+ T-cell reactivity is currently 
      uncertain.
CI  - (c) 2023 The Author(s). Published by Portland Press Limited on behalf of the 
      Biochemical Society.
FAU - Nicholas, Ben
AU  - Nicholas B
AD  - Centre for Proteomic Research, Biological Sciences and Institute for Life 
      Sciences, Building 85, University of Southampton, SO17 1BJ, U.K.
FAU - Skipp, Paul
AU  - Skipp P
AUID- ORCID: 0000-0003-1467-9643
AD  - Centre for Proteomic Research, Biological Sciences and Institute for Life 
      Sciences, Building 85, University of Southampton, SO17 1BJ, U.K.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - England
TA  - Essays Biochem
JT  - Essays in biochemistry
JID - 0043306
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA Antigens)
RN  - 0 (Antigens, Neoplasm)
SB  - IM
MH  - Humans
MH  - *Epitopes, T-Lymphocyte/metabolism
MH  - CD8-Positive T-Lymphocytes/metabolism
MH  - *Neoplasms/metabolism
MH  - HLA Antigens/metabolism
MH  - Antigens, Neoplasm/chemistry/metabolism
OTO - NOTNLM
OT  - T-cells
OT  - immunopeptidomics
OT  - mass spectrometry
OT  - neoantigen
EDAT- 2023/07/28 06:42
MHDA- 2023/10/23 12:42
CRDT- 2023/07/28 04:43
PHST- 2023/02/24 00:00 [received]
PHST- 2023/07/03 00:00 [revised]
PHST- 2023/07/13 00:00 [accepted]
PHST- 2023/10/23 12:42 [medline]
PHST- 2023/07/28 06:42 [pubmed]
PHST- 2023/07/28 04:43 [entrez]
AID - 233325 [pii]
AID - 10.1042/EBC20220246 [doi]
PST - ppublish
SO  - Essays Biochem. 2023 Sep 28;67(6):957-965. doi: 10.1042/EBC20220246.