arXiv subjects

Luis Almeida

Publications and source records attributed to Luis Almeida.

25 records · Page 2Linked to original sources

arXiv2021

A mathematical model to study the impact of intra-tumour heterogeneity on anti-tumour CD8+ T cell immune response

Intra-tumour heterogeneity (ITH) has a strong impact on the efficacy of the immune response against solid tumours. The number of sub-populations of cancer cells expressing different antigens and the percentage of immunogenic cells (i.e. tumour cells that are effectively targeted by immune cells) in a tumour are both expressions of ITH. Here, we present a spatially explicit stochastic individual-based model of the interaction dynamics between tumour cells and CD8+ T cells, which makes it possible to dissect out the specific impact of these two expressions of ITH on anti-tumour immune response. The set-up of numerical simulations of the model is defined so as to mimic scenarios considered in previous experimental studies. Moreover, the ability of the model to qualitatively reproduce experimental observations of successful and unsuccessful immune surveillance is demonstrated. First, the results of numerical simulations of this model indicate that the presence of a larger number of sub-populations of tumour cells that express different antigens is associated with a reduced ability of CD8+ T cells to mount an effective anti-tumour immune response. Second, the presence of a larger percentage of tumour cells that are not effectively targeted by CD8+ T cells may reduce the effectiveness of anti-tumour immunity. Ultimately, the mathematical model presented in this paper may provide a framework to help biologists and clinicians to better understand the mechanisms that are responsible for the emergence of different outcomes of immunotherapy.

q-bio.CB↗

arXiv2021

Treatment-induced shrinking of tumour aggregates: A nonlinear volume-filling chemotactic approach

Motivated by experimental observations in 3D/organoid cultures derived from glioblastoma, we develop a mathematical model where tumour aggregate formation is obtained as the result of nutrient-limited cell proliferation coupled with chemotaxis-based cell movement. The introduction of a chemotherapeutic treatment induces mechanical changes at the cell level, with cells undergoing a transition from rigid bodies to semi-elastic entities. We analyse the influence of these individual mechanical changes on the properties of the aggregates obtained at the population level by introducing a nonlinear volume-filling chemotactic system of partial differential equations. The elastic properties of the cells are taken into account through the so-called squeezing probability, which allows us to change the packing capacity of the aggregates, depending on the concentration of the treatment in the extracellular microenvironment. We explore two scenarios for the effect of the treatment: firstly, the treatment acts only on the mechanical properties of the cells and, secondly, we assume it also prevents cell proliferation. A linear stability analysis enables us to study the ability of the system to create patterns. We provide numerical simulations in 1D and 2D that illustrate the shrinking of the aggregates due to the presence of the treatment.

nlin.PS↗

arXiv2021

Analysis of the "Rolling carpet" strategy to eradicate an invasive species

In order to prevent the propagation of human diseases transmitted by mosquitoes (such as dengue or zika), one possible solution is to act directly on the mosquito population. In this work, we consider an invasive species (the mosquitoes) and we study two strategies to eradicate the population in the whole space by a local intervention. The dynamics of the population is modeled through a bistable reaction diffusion equation in an one dimensional setting and both strategies are based on the same idea : we act on a moving interval. The action of the first strategy is to kill as many individuals as we can in this moving interval. The action of the second strategy is to release sterile males in this moving interval. For both strategies, we manage to generate traveling waves that propagate in the opposite direction relative to the one of the natural invasive traveling wave. These cases correspond to succeeding in eradicating the invasive species. Furthermore, for the first strategy, we fully characterize the minimal size of the interval. All the results are illustrated by numerical simulations.

math.AP↗

arXiv2020

The sterile insect technique used as a barrier control against reinfestation

The sterile insect technique consists in massive release of sterilized males in the aim to reduce the size of mosquitoes population or even eradicate it. In this work, we investigate the feasability of using the sterile insect technique as a barrier against reinvasion. More precisely, we provide some numerical simulations and mathematical results showing that performing the sterile insect technique on a band large enough may stop reinvasion.

math.AP↗

arXiv2020

Minimal cost-time strategies for population replacement using the IIT

Vector control plays a central role in the fight against vector-borne diseases and, in particular, arboviruses. The use of the endosymbiotic bacterium Wolbachia has proven effective in preventing the transmission of some of these viruses between mosquitoes and humans, making it a promising control tool. The Incompatible Insect Technique (IIT) consists in replacing the wild population by a population carrying the aforementioned bacterium, thereby preventing outbreaks of the associated vector-borne diseases. In this work, we consider a two species model incorporating both Wolbachia infected and wild mosquitoes. Our system can be controlled thanks to a term representing an artificial introduction of Wolbachia-infected mosquitoes. Under the assumption that the birth rate of mosquitoes is high, we may reduce the model to a simpler one on the proportion of infected mosquitoes. We investigate minimal cost-time strategies to achieve a population replacement both analytically and numerically for the simplified 1D model and only numerically for the full 2D system

math.AP↗

arXiv2018

A chemotaxis-based explanation of spheroid formation in 3D cultures of breast cancer cells

Three-dimensional cultures of cells are gaining popularity as an in vitro improvement over 2D Petri dishes. In many such experiments, cells have been found to organize in aggregates. We present new results of three-dimensional in vitro cultures of breast cancer cells exhibiting patterns. Understanding their formation is of particular interest in the context of cancer since metastases have been shown to be created by cells moving in clusters. In this paper, we propose that the main mechanism which leads to the emergence of patterns is chemotaxis, i.e., oriented movement of cells towards high concentration zones of a signal emitted by the cells themselves. Studying a Keller-Segel PDE system to model chemotactical auto-organization of cells, we prove that it is subject to Turing instability under a time-dependent condition. This result is illustrated by two-dimensional simulations of the model showing spheroidal patterns. They are qualitatively compared to the biological results and their variability is discussed both theoretically and numerically.

q-bio.CB↗

arXiv2018

Oscillatory regimes in a mosquito population model with larval feedback on egg hatching

Understanding mosquitoes life cycle is of great interest presently because of the increasing impact of vector borne diseases in several countries. There is evidence of oscillations in mosquito populations independent of seasonality, still unexplained, based on observations both in laboratories and in nature. We propose a simple mathematical model of egg hatching enhancement by larvae which produces such oscillations that conveys a possible explanation. We propose both a theoretical analysis, based on slow-fast dynamics and Hopf bifurcation, and numerical investigations in order to shed some light on the mechanisms at work in this model.

math.DS↗