A nonlinear mathematical model of cell-mediated immune response for tumor phenotypic heterogeneity

Abstract

Human cancers display intra-tumor heterogeneity in many phenotypic features, such as expression of cell surface receptors, growth, and angiogenic, proliferative, and immunogenic factors, which represent obstacles to a successful immune response. In this paper, we propose a nonlinear mathematical model of cancer immunosurveillance that takes into account some of these features based on cell-mediated immune responses. The model describes phenomena that are seen in vivo, such as tumor dormancy, robustness, immunoselection over tumor heterogeneity (also called "cancer immunoediting") and strong sensitivity to initial conditions in the composition of tumor microenvironment. The results framework has as common element the tumor as an attractor for abnormal cells. Bifurcation analysis give us as tumor attractors fixed-points, limit cycles and chaotic attractors, the latter emerging from period-doubling cascade displaying Feigenbaum's universality. Finally, we simulated both elimination and escape tumor scenarios by means of a stochastic version of the model according to the Doob-Gillespie algorithm.

Keywords: Attractors; Bifurcations; Chaos; Doob-Gillespie; Immunoediting; Immunoselection.