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Abstract

In this study, we provide a dynamical systems perspective to the modelling of pathological
states induced by tumors or infection. A unified disease model is established using the innate
immune system as the reference point. We propose a two-layer network model for carcinogenesis
and sepsis based upon the interaction of parenchymal cells and immune cells via cytokines, and
the co-evolutionary dynamics of parenchymal, immune cells, and cytokines. Our aim is to show
that the complex cellular cooperation between parenchyma and stroma (immune layer) in the
physiological and pathological case can be qualitatively and functionally described by a simple
paradigmatic model of phase oscillators. By this, we explain carcinogenesis, tumor progression,
and sepsis by destabilization of the healthy homeostatic state (frequency synchronized), and
emergence of a pathological state (desynchronized or multifrequency cluster). The coupled
dynamics of parenchymal cells (metabolism) and nonspecific immune cells (reaction of innate
immune system) are represented by nodes of a duplex layer. The cytokine interaction is modeled
by adaptive coupling weights between the nodes representing the immune cells (with fast
adaptation time scale) and the parenchymal cells (slow adaptation time scale) and between
the pairs of parenchymal and immune cells in the duplex network (fixed bidirectional coupling).
Thereby, carcinogenesis, organ dysfunction in sepsis, and recurrence risk can be described in a
correct functional context.