Steele et al. found that C-X-C chemokine receptor type 2 (CXCR2) expression in neutrophils and myeloid-derived suppressor cells (MDSCs) at tumour borders correlates with poor prognosis in pancreatic ductal adenocarcinoma (PDAC). Genetic ablation and inhibition of CXCR2 in PDAC mouse models reduced metastasis but only inhibition slowed tumorigenesis, suggesting different roles for CXCR2 at different tumour stages. CXCR2 was also implicated in immune cell migration and metastatic niche establishment. CXCR2 blockade increased sensitivity to gemcitabine and programmed cell death protein 1 (PD1) antibodies, underscoring CXCR2 as a therapeutic target for late-stage PDAC.