Tumour-immune dynamics with an immune checkpoint inhibitor

Elpiniki Nikolopoulou
School of Mathematical & Statistical Sciences, Arizona State University, Tempe, AZ, USA

Lauren R. Johnson
School of Mathematical & Statistical Sciences, Arizona State University, Tempe, AZ, USA

Duane Harris
School of Mathematical & Statistical Sciences, Arizona State University, Tempe, AZ, USA

John D. Nagy
School of Mathematical & Statistical Sciences, Arizona State University, Tempe, AZ, USA Department of Biology, Scottsdale Community College, Scottsdale, AZ, USA

Edward C. Stites
Integrative Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA

Yang Kuang
School of Mathematical & Statistical Sciences, Arizona State University, Tempe, AZ, USA

Abstract

The use of immune checkpoint inhibitors is becoming more commonplace in clinical trials across the nation. Two important factors in the tumour-immune response are the checkpoint protein programmed death-1 (PD-1) and its ligand PD-L1. We propose a mathematical tumour-immune model using a system of ordinary differential equations to study dynamics with and without the use of anti-PD-1. A sensitivity analysis is conducted, and series of simulations are performed to investigate the effects of intermittent and continuous treatments on the tumour-immune dynamics. We consider the system without the anti-PD-1 drug to conduct a mathematical analysis to determine the stability of the tumour-free and tumorous equilibria. Through simulations, we found that a normally functioning immune system may control tumour. We observe treatment with anti-PD-1 alone may not be sufficient to eradicate tumour cells. Therefore, it may be beneficial to combine single agent treatments with additional therapies to obtain a better antitumour response.

Keywords: Immunotherapy ,Mathematical oncology ,Checkpoint inhibitor ,Tumour, PD-1 ,PD-L1 ,Anti-PD-1 ,Tumour/immune model

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