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A stochastic model for immunotherapy of cancer

We propose an extension of a standard stochastic individual-based model in population dynamics which broadens the range of biological applications. Our primary motivation is modelling of immunotherapy of malignant tumours. In this context the different actors, T-cells, cytokines or cancer cells, are...

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Autores principales: Baar, Martina, Coquille, Loren, Mayer, Hannah, Hölzel, Michael, Rogava, Meri, Tüting, Thomas, Bovier, Anton
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4827069/
https://www.ncbi.nlm.nih.gov/pubmed/27063839
http://dx.doi.org/10.1038/srep24169
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author Baar, Martina
Coquille, Loren
Mayer, Hannah
Hölzel, Michael
Rogava, Meri
Tüting, Thomas
Bovier, Anton
author_facet Baar, Martina
Coquille, Loren
Mayer, Hannah
Hölzel, Michael
Rogava, Meri
Tüting, Thomas
Bovier, Anton
author_sort Baar, Martina
collection PubMed
description We propose an extension of a standard stochastic individual-based model in population dynamics which broadens the range of biological applications. Our primary motivation is modelling of immunotherapy of malignant tumours. In this context the different actors, T-cells, cytokines or cancer cells, are modelled as single particles (individuals) in the stochastic system. The main expansions of the model are distinguishing cancer cells by phenotype and genotype, including environment-dependent phenotypic plasticity that does not affect the genotype, taking into account the effects of therapy and introducing a competition term which lowers the reproduction rate of an individual in addition to the usual term that increases its death rate. We illustrate the new setup by using it to model various phenomena arising in immunotherapy. Our aim is twofold: on the one hand, we show that the interplay of genetic mutations and phenotypic switches on different timescales as well as the occurrence of metastability phenomena raise new mathematical challenges. On the other hand, we argue why understanding purely stochastic events (which cannot be obtained with deterministic models) may help to understand the resistance of tumours to therapeutic approaches and may have non-trivial consequences on tumour treatment protocols. This is supported through numerical simulations.
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spelling pubmed-48270692016-04-19 A stochastic model for immunotherapy of cancer Baar, Martina Coquille, Loren Mayer, Hannah Hölzel, Michael Rogava, Meri Tüting, Thomas Bovier, Anton Sci Rep Article We propose an extension of a standard stochastic individual-based model in population dynamics which broadens the range of biological applications. Our primary motivation is modelling of immunotherapy of malignant tumours. In this context the different actors, T-cells, cytokines or cancer cells, are modelled as single particles (individuals) in the stochastic system. The main expansions of the model are distinguishing cancer cells by phenotype and genotype, including environment-dependent phenotypic plasticity that does not affect the genotype, taking into account the effects of therapy and introducing a competition term which lowers the reproduction rate of an individual in addition to the usual term that increases its death rate. We illustrate the new setup by using it to model various phenomena arising in immunotherapy. Our aim is twofold: on the one hand, we show that the interplay of genetic mutations and phenotypic switches on different timescales as well as the occurrence of metastability phenomena raise new mathematical challenges. On the other hand, we argue why understanding purely stochastic events (which cannot be obtained with deterministic models) may help to understand the resistance of tumours to therapeutic approaches and may have non-trivial consequences on tumour treatment protocols. This is supported through numerical simulations. Nature Publishing Group 2016-04-11 /pmc/articles/PMC4827069/ /pubmed/27063839 http://dx.doi.org/10.1038/srep24169 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Baar, Martina
Coquille, Loren
Mayer, Hannah
Hölzel, Michael
Rogava, Meri
Tüting, Thomas
Bovier, Anton
A stochastic model for immunotherapy of cancer
title A stochastic model for immunotherapy of cancer
title_full A stochastic model for immunotherapy of cancer
title_fullStr A stochastic model for immunotherapy of cancer
title_full_unstemmed A stochastic model for immunotherapy of cancer
title_short A stochastic model for immunotherapy of cancer
title_sort stochastic model for immunotherapy of cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4827069/
https://www.ncbi.nlm.nih.gov/pubmed/27063839
http://dx.doi.org/10.1038/srep24169
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