We propose an extension of a standard stochastic individual-based model in population dynamics which broadens the range of biological applications. Our primary motivation is modelling of immunotherapy of malignant tumours. In this context the different actors, T-cells, cytokines or cancer cells, are modelled as single particles (individuals) in the stochastic system. The main expansions of the model are distinguishing cancer cells by phenotype and genotype, including environment-dependent phenotypic plasticity that does not affect the genotype, taking into account the effects of therapy and introducing a competition term which lowers the reproduction rate of an individual in addition to the usual term that increases its death rate. We illustrate the new setup by using it to model various phenomena arising in immunotherapy. Our aim is twofold: on the one hand, we show that the interplay of genetic mutations and phenotypic switches on different timescales as well as the occurrence of metastability phenomena raise new mathematical challenges. On the other hand, we argue why understanding purely stochastic events (which cannot be obtained with deterministic models) may help to understand the resistance of tumours to therapeutic approaches and may have non-trivial consequences on tumour treatment protocols. This is supported through numerical simulations.

We consider a model for Darwinian evolution in an asexual population with a large but non-constant populations size characterized by a natural birth rate, a logistic death rate modelling competition and a probability of mutation at each birth event. In the present paper, we study the long-term behavior of the system in the limit of large population (K → ∞) size, rare mutations (u → 0), and small mutational effects (σ → 0), proving convergence to the canonical equation of adaptive dynamics (CEAD). In contrast to earlier works, e.g. by Champagnat and Méléard, we take the three limits simultaneously, i.e. u = u K and σ = σ K , tend to zero with K, subject to conditions that ensure that the time-scale of birth and death events remains separated from that of successful mutational events. This slows down the dynamics of the microscopic system and leads to serious technical difficulties that requires the use of completely different methods. In particular, we cannot use the law of large numbers on the diverging time needed for fixation to approximate the stochastic system with the corresponding deterministic one. To solve this problem we develop a "stochastic Euler scheme" based on coupling arguments that allows to control the time evolution of the stochastic system over time-scales that diverge with K.

In this paper we study a class of stochastic individual-based models that describe the evolution of haploid populations where each individual is characterised by a phenotype and a genotype. The phenotype of an individual determines its natural birth-and death rates as well as the competition kernel, c(x, y) which describes the induced death rate that an individual of type x experiences due to the presence of an individual or type y. When a new individual is born, with a small probability a mutation occurs, i.e. the offspring has different genotype as the parent. The novel aspect of the models we study is that an individual with a given genotype may express a certain set of different phenotypes, and during its lifetime it may switch between different phenotypes, with rates that are much larger then the mutation rates and that, moreover, may depend on the state of the entire population. The evolution of the population is described by a continuous-time, measure-valued Markov process. In [4], such a model was proposed to describe tumor evolution under immunotherapy. In the present paper we consider a large class of models which comprises the example studied in [4] and analyse their scaling limits as the population size tends to infinity and the mutation rate tends to zero. Under suitable assumptions, we prove convergence to a Markov jump process that is a generalisation of the polymorphic evolution sequence (PES) as analysed in [8,10].

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