Antigen processing and immune regulation in the response to tumours
Antigen processing and immune regulation in the response to tumours
The MHC class I and II antigen processing and presentation pathways display peptides to circulating CD8+ cytotoxic and CD4+ helper T cells respectively to enable pathogens and transformed cells to be identified. Once detected, T cells become activated and either directly kill the infected / transformed cells (CD8+ cytotoxic T lymphocytes) or orchestrate the activation of the adaptive immune response (CD4+ T cells). The immune surveillance of transformed/tumour cells drives alteration of the antigen processing and presentation pathways to evade detection and hence the immune response. Evasion of the immune response is a significant event tumour development and considered one of the hallmarks of cancer. To avoid immune recognition, tumours employ a multitude of strategies with most resulting in a down-regulation of the MHC class I expression at the cell surface, significantly impairing the ability of CD8+ cytotoxic T lymphocytes to recognize the tumour. Alteration of the expression of key players in antigen processing not only affects MHC class I expression but also significantly alters the repertoire of peptides being presented. These modified peptide repertoires may serve to further reduce the presentation of tumour-specific/associated antigenic epitopes to aid immune evasion and tumour progression. Here we review the modifications to the antigen processing and presentation pathway in tumours and how it affects the anti-tumour immune response, considering the role of tumour-infiltrating cell populations and highlighting possible future therapeutic targets.
16-24
Reeves, Emma
bd61ff0c-6555-47fd-884f-74dc6105e846
James, Edd
7dc1afb7-d326-4050-89fc-1f4e2a1a19a4
January 2017
Reeves, Emma
bd61ff0c-6555-47fd-884f-74dc6105e846
James, Edd
7dc1afb7-d326-4050-89fc-1f4e2a1a19a4
Abstract
The MHC class I and II antigen processing and presentation pathways display peptides to circulating CD8+ cytotoxic and CD4+ helper T cells respectively to enable pathogens and transformed cells to be identified. Once detected, T cells become activated and either directly kill the infected / transformed cells (CD8+ cytotoxic T lymphocytes) or orchestrate the activation of the adaptive immune response (CD4+ T cells). The immune surveillance of transformed/tumour cells drives alteration of the antigen processing and presentation pathways to evade detection and hence the immune response. Evasion of the immune response is a significant event tumour development and considered one of the hallmarks of cancer. To avoid immune recognition, tumours employ a multitude of strategies with most resulting in a down-regulation of the MHC class I expression at the cell surface, significantly impairing the ability of CD8+ cytotoxic T lymphocytes to recognize the tumour. Alteration of the expression of key players in antigen processing not only affects MHC class I expression but also significantly alters the repertoire of peptides being presented. These modified peptide repertoires may serve to further reduce the presentation of tumour-specific/associated antigenic epitopes to aid immune evasion and tumour progression. Here we review the modifications to the antigen processing and presentation pathway in tumours and how it affects the anti-tumour immune response, considering the role of tumour-infiltrating cell populations and highlighting possible future therapeutic targets.
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Antigen processing in cancer review revised + figures
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Reeves_et_al-2017-Immunology.pdf
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Accepted/In Press date: 19 September 2016
e-pub ahead of print date: 12 October 2016
Published date: January 2017
Organisations:
Cancer Sciences
Identifiers
Local EPrints ID: 405656
URI: http://eprints.soton.ac.uk/id/eprint/405656
ISSN: 0019-2805
PURE UUID: 429f77c6-415a-4104-b40a-f64d5387628f
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Date deposited: 10 Feb 2017 11:21
Last modified: 16 Mar 2024 03:51
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Author:
Emma Reeves
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