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

TL;DR

This paper introduces a hybrid discrete-continuum model to study how T-cell infiltration affects the immune response against tumors, providing insights into immune dynamics and potential immunotherapy impacts.

Contribution

The paper develops a novel hybrid modeling framework combining agent-based and continuum approaches, with a formal derivation and validation against purely continuum models.

Findings

Excellent agreement between hybrid and continuum models.

T-cell infiltration significantly influences tumor response to immunotherapy.

Mechanistic insights into immune-tumor interactions.

Abstract

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.