PMID- 35318648 OWN - NLM STAT- MEDLINE DCOM- 20220523 LR - 20230722 IS - 1365-2567 (Electronic) IS - 0019-2805 (Print) IS - 0019-2805 (Linking) VI - 166 IP - 2 DP - 2022 Jun TI - Tumour-associated antigenic peptides are present in the HLA class I ligandome of cancer cell line derived extracellular vesicles. PG - 249-264 LID - 10.1111/imm.13471 [doi] AB - The recent success of monoclonal antibody checkpoint inhibitor therapies that enhance the ability of CD8(+) T cells to detect cancer-related antigenic peptides has refocused the need to fully understand the repertoire of peptides being presented to the immune system. Whilst the peptide ligandome presented by cell surface human leucocyte antigen class I (HLA-I) molecules on cancer cells has been studied extensively, the ligandome of extracellular vesicles (EVs) remains poorly defined. Here, we report the HLA-I ligandome of both the cell surface and EVs from eight breast cancer cell lines (MCF7, MDA-MB-231, MDA-MB-361, MDA-MB-415, MDA-MB-453, HCC 1806, HCC 1395, and HCC 1954), and additionally the melanoma cell line ESTDAB-056 and the multiple myeloma line RPMI 8226. Utilizing HLA-I immunoisolation and mass spectrometry, we detected a total of 6574 peptides from the cell surface and 2461 peptides from the EVs of the cell lines studied. Within the EV HLA-I ligandome, we identified 150 peptides derived from tumour associated antigenic proteins, of which 19 peptides have been shown to elicit T-cell responses in previous studies. Our data thus show the prevalence of clinically relevant tumour-associated antigenic peptides in the HLA-I ligandome presented on EV. CI - (c) 2022 The Authors. Immunology published by John Wiley & Sons Ltd. FAU - Kumar, Pankaj AU - Kumar P AD - School of Medicine, University of St Andrews, St Andrews, UK. FAU - Boyne, Caitlin AU - Boyne C AD - School of Medicine, University of St Andrews, St Andrews, UK. FAU - Brown, Sydney AU - Brown S AD - School of Medicine, University of St Andrews, St Andrews, UK. FAU - Qureshi, Ayesha AU - Qureshi A AUID- ORCID: 0000-0003-0910-153X AD - School of Medicine, University of St Andrews, St Andrews, UK. FAU - Thorpe, Peter AU - Thorpe P AD - School of Medicine, University of St Andrews, St Andrews, UK. FAU - Synowsky, Silvia A AU - Synowsky SA AD - School of Biology, University of St Andrews, St Andrews, UK. AD - Biomedical Sciences Research Complex, University of St Andrews, St Andrews, UK. FAU - Shirran, Sally AU - Shirran S AD - School of Biology, University of St Andrews, St Andrews, UK. AD - Biomedical Sciences Research Complex, University of St Andrews, St Andrews, UK. FAU - Powis, Simon J AU - Powis SJ AUID- ORCID: 0000-0003-4218-2984 AD - School of Medicine, University of St Andrews, St Andrews, UK. AD - Biomedical Sciences Research Complex, University of St Andrews, St Andrews, UK. LA - eng GR - WT_/Wellcome Trust/United Kingdom GR - 105621/Z/14/Z/WT_/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220420 PL - England TA - Immunology JT - Immunology JID - 0374672 RN - 0 (Antigens, Neoplasm) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Ligands) RN - 0 (Peptides) SB - IM MH - Antigens, Neoplasm MH - CD8-Positive T-Lymphocytes MH - *Carcinoma, Hepatocellular/metabolism MH - Cell Line MH - *Extracellular Vesicles MH - Histocompatibility Antigens Class I/metabolism MH - Humans MH - Ligands MH - *Liver Neoplasms/metabolism MH - Peptides PMC - PMC10357481 OTO - NOTNLM OT - HLA ligandome OT - T-cell epitopes OT - breast cancer OT - extracellular vesicles OT - tumour associated antigen (TAA) COIS- The authors declare no conflicts of interest. EDAT- 2022/03/24 06:00 MHDA- 2022/05/24 06:00 PMCR- 2022/04/20 CRDT- 2022/03/23 05:49 PHST- 2021/12/16 00:00 [revised] PHST- 2021/09/22 00:00 [received] PHST- 2022/01/17 00:00 [accepted] PHST- 2022/03/24 06:00 [pubmed] PHST- 2022/05/24 06:00 [medline] PHST- 2022/03/23 05:49 [entrez] PHST- 2022/04/20 00:00 [pmc-release] AID - IMM13471 [pii] AID - 10.1111/imm.13471 [doi] PST - ppublish SO - Immunology. 2022 Jun;166(2):249-264. doi: 10.1111/imm.13471. Epub 2022 Apr 20.