We present a hybrid cellular automata-partial differential equation model of moderate complexity to describe the interactions between a growing tumor next to a nutrient source and the immune system of the host organism. The model allows both temporal and two-dimensional spatial evolution of the system under investigation and is comprised of biological cell metabolism rules derived from both the experimental and mathematical modeling literature. We present numerical simulations that display behaviors which are qualitatively similar to those exhibited in tumor-immune system interaction experiments. These include spherical tumor growth, stable and unstable oscillatory tumor growth, satellitosis and tumor infiltration by immune cells. Finally, the relationship between these different growth regimes and key system parameters is discussed.

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In this paper, we carry out an examination of four mechanisms that can potentially lead to changing morphologies in a growing tumor: variations in nutrient consumption rates, cellular adhesion, excessive consumption of nutrients by tumor cells and immune cell interactions with the tumor. We present numerical simulations using a hybrid PDE-cellular automata (CA) model demonstrating the effects of each mechanism before discussing hypotheses about the contribution of each mechanism to morphology change.

A distinct calcium profile is strongly implicated in regulating the multi-layered structure of the epidermis. However, the mechanisms that govern the regulation of this calcium profile are currently unclear. It clearly depends on the relatively impermeable barrier of the stratum corneum (passive regulation) but may also depend on calcium exchanges between keratinocytes and extracellular fluid (active regulation). Using a mathematical model that treats the viable sublayers of unwounded human and murine epidermis as porous media and assumes that their calcium profiles are passively regulated, we demonstrate that these profiles are also actively regulated. To obtain this result, we found that diffusion governs extracellular calcium motion in the viable epidermis and hence intracellular calcium is the main source of the epidermal calcium profile. Then, by comparison with experimental calcium profiles and combination with a hypothesised cell velocity distribution in the viable epidermis, we found that the net influx of calcium ions into keratinocytes from extracellular fluid may be constant and positive throughout the stratum basale and stratum spinosum, and that there is a net outflux of these ions in the stratum granulosum. Hence, the calcium exchange between keratinocytes and extracellular fluid differs distinctly between the stratum granulosum and the underlying sublayers, and these differences actively regulate the epidermal calcium profile. Our results also indicate that plasma membrane dysfunction may be an early event during keratinocyte disintegration in the stratum granulosum.