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A hybrid discrete-continuum modelling approach to explore the impact of T-cell infiltration on anti-tumour immune response

Authors :
Almeida, Luis
Audebert, Chloe
Leschiera, Emma
Lorenzi, Tommaso
Laboratoire Jacques-Louis Lions (LJLL (UMR_7598))
Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Modelling and Analysis for Medical and Biological Applications (MAMBA)
Inria de Paris
Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Jacques-Louis Lions (LJLL (UMR_7598))
Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Mathematical Modeling in Biology [LCQB] (LCQB-MMB)
Biologie Computationnelle et Quantitative = Laboratory of Computational and Quantitative Biology (LCQB)
Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS)
Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS)
Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Department of Mathematical Sciences [Torino] (DISMA)
Politecnico di Torino = Polytechnic of Turin (Polito)
E.L. has received funding from the European Research Council (ERC) under the European Union’s Horizon2020 research and innovation programme (grant agreement No 740623).T.L. gratefully acknowledges support from the Italian Ministry of University and Research (MUR) through the grant'Dipartimenti di Eccellenza 2018-2022' (Project no. E11G18000350001) and the PRIN 2020 project (No. 2020JLWP23)'Integrated Mathematical Approaches to Socio–Epidemiological Dynamics' (CUP: E15F21005420006).L.A., E.L. and T.L. gratefully acknowledge support from the CNRS International Research Project 'Modélisationde la biomécanique cellulaire et tissulaire' (MOCETIBI).
European Project: 740623,H2020 Pilier ERC,ADORA(2017)
Leschiera, Emma
Asymptotic approach to spatial and dynamical organizations - ADORA - - H2020 Pilier ERC2017-09-01 - 2022-08-31 - 740623 - VALID
Source :
Bulletin of Mathematical Biology, Bulletin of Mathematical Biology, In press
Publication Year :
2022
Publisher :
HAL CCSD, 2022.

Abstract

International audience; We present a spatial hybrid discrete-continuum modelling framework for the interaction dynamics between tumour cells and cytotoxic T cells, which play a pivotal role in the immune response against tumours. In this framework, tumour cells and T cells are modelled as individual agents while chemokines that drive the chemotactic movement of T cells towards the tumour are modelled as a continuum. We formally derive the continuum counterpart of this model, which is given by a coupled system that comprises an integro-differential equation for the density of tumour cells, a partial differential equation for the density of T cells, and a partial differential equation for the concentration of chemokines. We report on computational results of the hybrid model and show that there is an excellent quantitative agreement between them and numerical solutions of the corresponding continuum model. These results shed light on the mechanisms that underlie the emergence of different levels of infiltration of T cells into the tumour and elucidate how T-cell infiltration shapes anti-tumour immune response. Moreover, to present a proof of concept for the idea that, exploiting the computational efficiency of the continuum model, extensive numerical simulations could be carried out, we investigate the impact of T-cell infiltration on the response of tumour cells to different types of anti-cancer immunotherapy.

Details

Language :
English
ISSN :
00928240 and 15229602
Database :
OpenAIRE
Journal :
Bulletin of Mathematical Biology, Bulletin of Mathematical Biology, In press
Accession number :
edsair.doi.dedup.....8051cd61649febf6cc2031c18a23bc5c