English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

We study a five-compartment mathematical model originally proposed byKuznetsov et al. (1994) to investigate the effect of nonlinear interactionsbetween tumour and immune cells in the tumour microenvironment, whereby immunecells may induce tumour cell death, and tumour cells may inactivate immunecells. Exploiting a separation of timescales in the model, we use the method ofmatched asymptotics to derive a new two-dimensional, long-timescale,approximation of the full model, which differs from the quasi-steady-stateapproximation introduced by Kuznetsov et al. (1994), but is validated againstnumerical solutions of the full model. Through a phase-plane analysis, we showthat our reduced model is excitable, a feature not traditionally associatedwith tumour-immune dynamics. Through a systematic parameter sensitivityanalysis, we demonstrate that excitability generates complex bifurcatingdynamics in the model. These are consistent with a variety of clinicallyobserved phenomena, and suggest that excitability may underpin tumour-immuneinteractions. The model exhibits the three stages of immunoediting -elimination, equilibrium, and escape, via stable steady states with differenttumour cell concentrations. Such heterogeneity in tumour cell numbers can stemfrom variability in initial conditions and/or model parameters that control theproperties of the immune system and its response to the tumour. We identifydifferent biophysical parameter targets that could be manipulated withimmunotherapy in order to control tumour size, and we find that preferredstrategies may differ between patients depending on the strength of theirimmune systems, as determined by patient-specific values of associated modelparameters.

Identifying and characterising the impact of excitability in a mathematical model of tumour-immune interactions