Epigenetic Plasticity
in Tumour–Immune Ecosystems

Multiscale modelling from cellular state transitions to nonlocal interactions

Cancer cells are not characterised only by genetic mutations. They can also dynamically modify their phenotype in response to environmental signals, therapeutic pressure, and interactions with neighbouring cells. This epigenetic plasticity plays a fundamental role in invasion, treatment resistance, metastatic potential, and immune escape.

One major direction of this project concerns the transition between epithelial and mesenchymal phenotypes, including epithelial-to-mesenchymal transition (EMT) and its reverse process. Rather than describing these states as fixed populations, I develop mathematical models in which individual cells can dynamically move across a continuum of phenotypic states.

A key objective is to understand how molecular-scale variations can generate observable changes at the population and tissue level. I therefore work on multiscale mathematical models that connect microscopic processes — such as changes in the expression of specific proteins or regulatory pathways — with cellular phenotypes and, ultimately, with macroscopic tumour behaviour. This provides a framework to investigate how alterations at the molecular scale can influence proliferation, motility, invasion, and population structure.

A second direction focuses on the interaction between epigenetic tumour states and the immune microenvironment. Tumour cells, immune cells, stromal components, cytokines, growth factors, and extracellular matrix signals interact across different spatial ranges. To represent these processes, I investigate models involving nonlocal interactions, in which the behaviour of a cell depends not only on its immediate neighbours but also on signals generated throughout its surrounding environment.

The aim is to derive mathematically tractable macroscopic descriptions from biologically meaningful microscopic interaction rules, allowing us to study how local cellular plasticity can generate large-scale phenomena such as tumour invasion, immune evasion, spatial pattern formation, dormancy, or progression.

This research includes collaborations with Politecnico di Torino and with Prof. José A. Carrillo and the Mathematical Biology group at the Mathematical Institute, University of Oxford.

Main themes: epigenetic plasticity · EMT/MET · tumour heterogeneity · tumour–immune interactions · multiscale modelling · kinetic and continuum models · nonlocal interactions · mathematical biology · phenotype dynamics