Speaker
Description
Tertiary lymphoid structures (TLSs) are organised immune aggregates composed of T- and B-cells that form in tumours and are associated with improved patient outcomes. They develop from initially well-mixed lymphocyte populations into spatially organised structures. The mechanisms governing this process remain poorly understood, and there is no clear quantitative framework to relate TLS spatial organisation to underlying cellular processes.
We combine spatial analysis of experimental data with agent-based modelling to study TLS dynamics. We apply spatial statistics, including cross pair correlation functions and Moran’s I, to quantify cell–cell colocalisation and organisation in spatial transcriptomic data. This reveals a maturation axis from well-mixed aggregates to segregated B- and T-cell zones.
Motivated by these observations, we develop an on-lattice agent-based model in which T- and B-cells migrate in response to chemokine signals from stromal cells. Feedback between lymphocytes and stromal cells drives the emergence of spatially segregated TLS organisation.
Finally, we integrate these approaches by applying the same spatial metrics to model simulations, projecting simulations onto the inferred maturation axis. This provides a quantitative framework for linking observed TLS structure to underlying cellular mechanisms.
