Neutrophils in cancer: Insights from intravital imaging
TL;DR
This mini-review spotlights intravital imaging approaches that illuminate neutrophil dynamics in tumours and discusses how extrinsic regulators, including cancer-associated fibroblasts and neural inputs, direct neutrophil dynamics, further contributing to TME complexity.
Abstract
Multiple clinical and translational studies have shown that infiltration of tumour-associated neutrophils is associated with advanced disease stages, increased metastatic spread, therapeutic resistance, and poorer overall survival across various cancer types. Beyond their traditional role as first responders to tissue damage and pathogen infection, neutrophils within the tumour microenvironment (TME) display remarkable functional plasticity, adopting phenotypes that can promote angiogenesis, extracellular matrix remodelling, immune suppression, and tumour cell invasion. Importantly, it is now recognised that the prognostic impact of neutrophils is highly context-dependent, shaped by tumour type, stage, and the evolving inflammatory milieu. Intravital imaging studies have revealed dynamic neutrophil behaviours, including distinct migratory patterns between intra-tumoural and peri-tumoural regions, interactions with tumour and immune cells, and contributions to processes such as metastasis and immune suppression. However, there is a lack of understanding of how transcriptionally defined neutrophil subsets translate into specific functional and behavioural states in the TME in vivo. This mini-review spotlights intravital imaging approaches that illuminate neutrophil dynamics in tumours. We also discuss how extrinsic regulators, including cancer-associated fibroblasts and neural inputs, direct neutrophil dynamics, further contributing to TME complexity.