A model of the effects of cancer cell motility and cellular adhesion properties on tumour-immune dynamics.
We present a three-dimensional model simulating the dynamics of an anti-cancer T-cell response against a small, avascular, early-stage tumour. Interactions at the tumour site are accounted for using an agent-based model (ABM), while immune cell dynamics in the lymph node are modelled as a system of delay differential equations (DDEs). We combine these separate approaches into a two-compartment hybrid ABM-DDE system to capture the T-cell response against the tumour. In the ABM at the tumour site, movement of tumour cells is modelled using effective physical forces with a specific focus on cell-to-cell adhesion properties and varying levels of tumour cell motility, thus taking into account the ability of cancer cells to spread and form clusters. We consider the effectiveness of the immune response over a range of parameters pertaining to tumour cell motility, cell-to-cell adhesion strength and growth rate. We also investigate the dependence of outcomes on the distribution of tumour cells. Low tumour cell motility is generally a good indicator for successful tumour eradication before relapse, while high motility leads, almost invariably, to relapse and tumour escape. In general, the effect of cell-to-cell adhesion on prognosis is dependent on the level of tumour cell motility, with an often unpredictable cross influence between adhesion and motility, which can lead to counterintuitive effects. In terms of overall tumour shape and structure, the spatial distribution of cancer cells in clusters of various sizes has shown to be strongly related to the likelihood of extinction.
Faculty of Science, Engineering and Technology, Department of Mathematics, Swinburne University of Technology, Melbourne, Victoria, Australia.
Federico
F
Frascoli
School of Applied Sciences, RMIT University, Melbourne, Victoria, Australia.
Emelie
E
Flood
School of Mathematics and Statistics, University of Sydney, New South Wales, Australia.
Peter S
PS
Kim
D019496:Cancer Vaccines / Q000627:therapeutic use; D002448:Cell Adhesion / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D003198:Computer Simulation; D006801:Humans; D055641:Mathematical Concepts; D018448:Models, Immunological; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D019496:Cancer Vaccines
cancer; dynamical systems; immunotherapy; mathematical biology