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Modelling the interplay between the CD4[Formula: see text] /CD8[Formula: see text] T-cell ratio and the expression of MHC-I in tumours

Describing the anti-tumour immune response as a series of cellular kinetic reactions from known immunological mechanisms, we create a mathematical model that shows the CD4[Formula: see text] /CD8[Formula: see text] T-cell ratio, T-cell infiltration and the expression of MHC-I to be interacting facto...

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Autores principales: Hurry, Christian John, Mozeika, Alexander, Annibale, Alessia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213681/
https://www.ncbi.nlm.nih.gov/pubmed/34143314
http://dx.doi.org/10.1007/s00285-021-01622-1
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author Hurry, Christian John
Mozeika, Alexander
Annibale, Alessia
author_facet Hurry, Christian John
Mozeika, Alexander
Annibale, Alessia
author_sort Hurry, Christian John
collection PubMed
description Describing the anti-tumour immune response as a series of cellular kinetic reactions from known immunological mechanisms, we create a mathematical model that shows the CD4[Formula: see text] /CD8[Formula: see text] T-cell ratio, T-cell infiltration and the expression of MHC-I to be interacting factors in tumour elimination. Methods from dynamical systems theory and non-equilibrium statistical mechanics are used to model the T-cell dependent anti-tumour immune response. Our model predicts a critical level of MHC-I expression which determines whether or not the tumour escapes the immune response. This critical level of MHC-I depends on the helper/cytotoxic T-cell ratio. However, our model also suggests that the immune system is robust against small changes in this ratio. We also find that T-cell infiltration and the specificity of the intra-tumour TCR repertoire will affect the critical MHC-I expression. Our work suggests that the functional form of the time evolution of MHC-I expression may explain the qualitative behaviour of tumour growth seen in patients.
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spelling pubmed-82136812021-07-01 Modelling the interplay between the CD4[Formula: see text] /CD8[Formula: see text] T-cell ratio and the expression of MHC-I in tumours Hurry, Christian John Mozeika, Alexander Annibale, Alessia J Math Biol Article Describing the anti-tumour immune response as a series of cellular kinetic reactions from known immunological mechanisms, we create a mathematical model that shows the CD4[Formula: see text] /CD8[Formula: see text] T-cell ratio, T-cell infiltration and the expression of MHC-I to be interacting factors in tumour elimination. Methods from dynamical systems theory and non-equilibrium statistical mechanics are used to model the T-cell dependent anti-tumour immune response. Our model predicts a critical level of MHC-I expression which determines whether or not the tumour escapes the immune response. This critical level of MHC-I depends on the helper/cytotoxic T-cell ratio. However, our model also suggests that the immune system is robust against small changes in this ratio. We also find that T-cell infiltration and the specificity of the intra-tumour TCR repertoire will affect the critical MHC-I expression. Our work suggests that the functional form of the time evolution of MHC-I expression may explain the qualitative behaviour of tumour growth seen in patients. Springer Berlin Heidelberg 2021-06-18 2021 /pmc/articles/PMC8213681/ /pubmed/34143314 http://dx.doi.org/10.1007/s00285-021-01622-1 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Hurry, Christian John
Mozeika, Alexander
Annibale, Alessia
Modelling the interplay between the CD4[Formula: see text] /CD8[Formula: see text] T-cell ratio and the expression of MHC-I in tumours
title Modelling the interplay between the CD4[Formula: see text] /CD8[Formula: see text] T-cell ratio and the expression of MHC-I in tumours
title_full Modelling the interplay between the CD4[Formula: see text] /CD8[Formula: see text] T-cell ratio and the expression of MHC-I in tumours
title_fullStr Modelling the interplay between the CD4[Formula: see text] /CD8[Formula: see text] T-cell ratio and the expression of MHC-I in tumours
title_full_unstemmed Modelling the interplay between the CD4[Formula: see text] /CD8[Formula: see text] T-cell ratio and the expression of MHC-I in tumours
title_short Modelling the interplay between the CD4[Formula: see text] /CD8[Formula: see text] T-cell ratio and the expression of MHC-I in tumours
title_sort modelling the interplay between the cd4[formula: see text] /cd8[formula: see text] t-cell ratio and the expression of mhc-i in tumours
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213681/
https://www.ncbi.nlm.nih.gov/pubmed/34143314
http://dx.doi.org/10.1007/s00285-021-01622-1
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