SORA

Advancing, promoting and sharing knowledge of health through excellence in teaching, clinical practice and research into the prevention and treatment of illness

Gemcitabine alters the proteasome composition and immunopeptidome of tumour cells

Gravett, AM; Trautwein, N; Stevanovic, S; Dalgleish, AG; Copier, J (2018) Gemcitabine alters the proteasome composition and immunopeptidome of tumour cells. OncoImmunology, 7 (6). e1438107. ISSN 2162-402X https://doi.org/10.1080/2162402X.2018.1438107
SGUL Authors: Gravett, Andrew Michael

[img]
Preview
PDF Published Version
Available under License Creative Commons Attribution Non-commercial No Derivatives.

Download (3MB) | Preview

Abstract

The antigenic makeup of tumour cells can have a profound effect on the progression of cancer and success of immunotherapies. Therefore, one strategy to improve the efficacy of cancer treatments is to augment the antigens displayed by tumours. The present study explores how the recognition of tumour cells may be altered by non-cytotoxic concentrations of gemcitabine (GEM). Testing a panel of chemotherapeutics in human cancer cell lines in vitro, it was found that GEM increased surface expression of HLA-A,B,C and that underlying this were specific increases in β-2-microglobulin and immunoproteasome subunit proteins. Furthermore, the peptide antigen repertoire displayed on HLA class I was altered, revealing a number of novel antigens, many of which that were derived from proteins involved in the DNA-damage response. Changes in the nature of the peptide antigens eluted from HLA-A,B,C after GEM treatment consisted of amino acid anchor-residue modifications and changes in peptide length which rendered peptides likely to favour alternative HLA-alleles and increased their predicted immunogenicity. Signalling through the MAPK/ERK and NFκB/RelB pathways was associated with these changes. These data may explain observations made in previous in vivo studies, advise as to which antigens should be used in future vaccination protocols and reinforce the idea that chemotherapy and immunotherapy could be used in combination.

Item Type: Article
Additional Information: © 2018 The Author(s). Published with license by Taylor & Francis Group, LLC© A. M. Gravett, N. Trautwein, S. Stevanović, A. G. Dalgleish and J. Copier This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: OncoImmunology
ISSN: 2162-402X
Dates:
DateEvent
6 March 2018Published Online
2 February 2018Accepted
Publisher License: Creative Commons: Attribution-Noncommercial-No Derivative Works 4.0
Projects:
Project IDFunderFunder ID
SFB 685Deutsche Forschungsgemeinschafthttp://dx.doi.org/10.13039/501100001659
URI: https://openaccess.sgul.ac.uk/id/eprint/109740
Publisher's version: https://doi.org/10.1080/2162402X.2018.1438107

Actions (login required)

Edit Item Edit Item