In silico tumor control induced via alternating immunostimulating and immunosuppressive phases

TL;DR

This paper develops a mathematical model to understand tumor-immune interactions and proposes a control strategy involving alternating immunostimulating and immunosuppressive phases to achieve long-term tumor control.

Contribution

It introduces a novel multiscale analysis and a theory-driven intervention strategy based on bifurcation analysis of tumor-immune dynamics.

Findings

Identification of parameter regimes for immune-mediated tumor control

Derivation of a harmonic oscillator approximation for tumor-immune dynamics

Proposal of alternating immune phases to induce tumor control

Abstract

Despite recent advances in the field of Oncoimmunology, the success potential of immunomodulatory therapies against cancer remains to be elucidated. One of the reasons is the lack of understanding on the complex interplay between tumor growth dynamics and the associated immune system responses. Towards this goal, we consider a mathematical model of vascularized tumor growth and the corresponding effector cell recruitment dynamics. Bifurcation analysis allows for the exploration of model's dynamic behavior and the determination of these parameter regimes that result in immune-mediated tumor control. Here, we focus on a particular tumor evasion regime that involves tumor and effector cell concentration oscillations of slowly increasing and decreasing amplitude, respectively. Considering a temporal multiscale analysis, we derive an analytically tractable mapping of model solutions onto a weakly negatively damped harmonic oscillator. Based on our analysis, we propose a theory-driven intervention strategy involving immunostimulating and immunosuppressive phases to induce long-term tumor control.