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Tumour-associated antigenic peptides are present in the HLA class I ligandome of cancer cell line derived extracellular vesicles

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Kumar_2022_Tumour_associated_antigenic_Immunology_13471_CCBY.pdf (2.210Mb)
Date
01/06/2022
Author
Kumar, Pankaj
Boyne, Caitlin
Brown, Sydney Erin
Qureshi, Ayesha
Thorpe, Peter Jacob
Synowsky, Silvia Anna
Shirran, Sally Lorna
Powis, Simon John
Funder
The Wellcome Trust
Grant ID
105621/Z/14/Z
Keywords
Extracellular vesicles
Tumour associated antigen (TAA)
HLA ligandome
T-cell epitopes
Breast cancer
QR180 Immunology
DAS
MCC
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Abstract
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. Utilising 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 shows the prevalence of clinically relevant tumour-associated antigenic peptides in the HLA-I ligandome presented on EV.
Citation
Kumar , P , Boyne , C , Brown , S E , Qureshi , A , Thorpe , P J , Synowsky , S A , Shirran , S L & Powis , S J 2022 , ' Tumour-associated antigenic peptides are present in the HLA class I ligandome of cancer cell line derived extracellular vesicles ' , Immunology , vol. 166 , no. 2 , 13471 , pp. 249-264 . https://doi.org/10.1111/imm.13471
Publication
Immunology
Status
Peer reviewed
DOI
https://doi.org/10.1111/imm.13471
ISSN
0019-2805
Type
Journal article
Rights
Copyright © 2022 The Authors. Immunology published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Description
Funding: Breast Cancer Now (Grant Number(s): 2018JulPR1086), Wellcome Trust (GrantNumber(s): 105621/Z/14/Z), Melville Charitable Trust.
Collections
  • University of St Andrews Research
URI
http://hdl.handle.net/10023/25221

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