Speaker
Description
Neutrophils are the most abundant circulating leukocytes and first responders to infection and tissue injury. Once viewed as short-lived and homogeneous, they are now recognised as a dynamically reconfigurable immune compartment with connected phenotypic and functional states in homeostasis and disease [1]. In this talk, I will present various modelling and high-dimensional data-driven approaches that we have developed at the Mathematical Oncology Laboratory in close collaboration with other biomedical institutions [2-5], to decode neutrophil behaviour across sterile inflammation, infection and cancer. Data-driven state-space ‘behavioural landscapes’ from intravital microscopy reveal stereotyped migratory states and pathogenic vascular-associated programmes that can be pharmacologically tuned [2]. Age-structured PDE models linked to fate-mapping quantify tissue-dependent neutrophil lifetimes and predict prolonged persistence within tumours [3]. Single-cell trajectories support deterministic reprogramming of tumour-infiltrating neutrophils towards pro-angiogenic, immunosuppressive niches [4]. Finally, the transcriptomic compartment architecture (NeuMap) integrates multi-tissue single-cell atlases with dynamical modelling to map perturbation-specific trajectories and nominate regulators of effector programmes [5]. Together, these approaches provide mathematical tools to study neutrophil plasticity and a framework to rationally target neutrophil states in infection and disease.
Bibliography
[1] Ng LG, Ballesteros I, Cassatella MA, Egeblad M, Fridlender ZG, Gabrilovich DI, et al. From complexity to consensus: A roadmap for neutrophil classification. Immunity (2025). doi:10.1016/j.immuni.2025.07.011.
[2] Crainiciuc G, Palomino-Segura M, Molina-Moreno M, et al. Behavioural immune landscapes of inflammation. Nature 601, 415–421 (2022). doi:10.1038/s41586-021-04263-y.
[3] Maas M, Chong W, Kwok I, et al. The local microenvironment drives activation of neutrophils in human brain tumours. Cell 186, 4546–4566 (2023). doi:10.1016/j.cell.2023.08.043.
[4] Ng MSF, Kwok I, Tan L, et al. Deterministic reprogramming of neutrophils within tumors. Science 383, eadf6493 (2024). doi:10.1126/science.adf6493.
[5] Cerezo-Wallis D, Kwok I, Ng MSF, et al. Architecture of the neutrophil compartment. Nature 649, 1003–1012 (2026). doi:10.1038/s41586-025-09807-0
