Profiling and targeting neutrophils in the setting of chromosomally unstable cancers

This project will investigate how chromosomal instability (CIN) shapes systemic and tumour-associated myeloid responses in oesophagogastric cancer (OGC), with a particular focus on neutrophil-driven immunosuppression as a therapeutic target. Building on the hypothesis that CIN promotes a targetable, immunosuppressive myeloid infiltrate, the work will combine longitudinal patient sampling with high-dimensional immune profiling to characterise circulating and tumour-resident myeloid populations at baseline and during chemo-immunotherapy. Using matched tumour and blood samples, CIN status will be quantified via cGAS-positive micronuclei, and correlated with dynamic changes in circulating immune cells and chemokine profiles to identify biomarkers of treatment response and resistance. Parallel analyses in novel CIN-high and CIN-low mouse models will enable mechanistic dissection and testing of strategies to therapeutically target myeloid-mediated immunosuppression. Together, this work aims to define clinically actionable biomarkers and vulnerabilities in CIN-high cancers, enabling earlier patient stratification and more effective, personalised treatment approaches.