Game-theoretical description of the go-or-grow dichotomy in tumor development for various settings and parameter constellations.

A medically important feature of several types of tumors is their ability to "decide" between staying at a primary site in the body or leaving it and forming metastases. The present theoretical study aims to provide a better understanding of the ultimate reasons for this so-called "go-or-grow" dichotomy. To that end, we use game theory, which has proven to be useful in analyzing the competition between tumors and healthy tissues or among different tumor cells. We begin by determining the game types in the Basanta-Hatzikirou-Deutsch model, depending on the parameter values. Thereafter, we suggest and analyze five modified variants of the model. For example, in the basic model, the deadlock game, Prisoner's Dilemma, and hawk-dove game can occur. The modified versions lead to several additional game types, such as battle of the sexes, route-choice, and stag-hunt games. For some game types, all cells are predicted to stay on their original site ("grow phenotype"), while for other types, only a certain fraction stay and the other cells migrate away ("go phenotype"). If the nutrient supply at a distant site is high, all the cells are predicted to go. We discuss our predictions in terms of the pros and cons of caloric restriction and limitations of the supply of vitamins or methionine. Our results may help devise treatments to prevent metastasis.

Molecular crypsis by pathogenic fungi using human factor H. A numerical model.

Molecular mimicry is the formation of specific molecules by microbial pathogens to avoid recognition and attack by the immune system of the host. Several pathogenic Ascomycota and Zygomycota show such a behaviour by utilizing human complement factor H to hide in the blood stream. We call this type of mimicry molecular crypsis. Such a crypsis can reach a point where the immune system can no longer clearly distinguish between self and non-self cells. Thus, a trade-off between attacking disguised pathogens and erroneously attacking host cells has to be made. Based on signalling theory and protein-interaction modelling, we here present a mathematical model of molecular crypsis of pathogenic fungi using the example of Candida albicans. We tackle the question whether perfect crypsis is feasible, which would imply that protection of human cells by complement factors would be useless. The model identifies pathogen abundance relative to host cell abundance as the predominant factor influencing successful or unsuccessful molecular crypsis. If pathogen cells gain a (locally) quantitative advantage over host cells, even autoreactivity may occur. Our new model enables insights into the mechanisms of candidiasis-induced sepsis and complement-associated autoimmune diseases.

Playing 'hide-and-seek' with factor H: game-theoretical analysis of a single nucleotide polymorphism.

As a part of the complement system, factor H regulates phagocytosis and helps differentiate between a body's own and foreign cells. Owing to mimicry efforts, some pathogenic microorganisms such as Candida albicans are able to bind factor H on their cell surfaces and, thus, become similar to host cells. This implies that the decision between self and foreign is not clear-cut, which leads to a classification problem for the immune system. Here, two different alleles determining the binding affinity of factor H are relevant. Those alleles differ in the SNP Y402H; they are known to be associated with susceptibility to certain diseases. Interestingly, the fraction of both alleles differs in ethnic groups. The game-theoretical model proposed in this article explains the coexistence of both alleles by a battle of the sexes game and investigates the trade-off between pathogen detection and protection of host cells. Further, we discuss the ethnicity-dependent frequencies of the alleles. Moreover, the model elucidates the mimicry efforts by pathogenic microorganisms.