Abstract PR10: CXCR2 Inhibition Suppresses Metastasis and Improves the Response to Immunotherapy in Pancreatic Cancer

Abstract

Abstract PDAC is predicted to become the second commonest cause of cancer death in the western world by 2030. Aggressive invasion and early metastases are characteristic of the disease, and even the few patients eligible for potentially curative resection inevitably develop recurrent or metastatic disease. We now show that CXCR2 signalling is upregulated in human pancreatic cancer, predominantly in neutrophils at the tumour invasive edge. In mouse models, genetic ablation or inhibition of CXCR2 abrogated metastasis while inhibition also slowed tumorigenesis, particularly when combined with chemotherapy. Depletion of neutrophils also suppressed metastasis, suggesting a key role for CXCR2 in establishing and maintaining the metastatic niche. Indications from trials thus far suggest that immunotherapy will not work as a single agent strategy in pancreatic cancer patients. Importantly, we find that loss or inhibition of CXCR2 improved T-cell entry and combined inhibition of CXCR2 and PD1 in mice with established disease caused a significant extension of survival. Thus, our data highlight two novel therapeutic opportunities for PDAC: first the use of CXCR2 inhibitors in surgically-resected patients to prevent recurrence at distant sites, and second, the use of CXCR2 inhibition in combination with immunotherapy in surgically unresectable advanced disease. This abstract is also being presented as Poster B55 Citation Format: Colin Steele, Saadia Karim, Josh Leach, Peter Bailey, Andrew Biankin, Rob Nibbs, Simon Barry, Owen Sansom, Jen Morton.{Authors}. CXCR2 Inhibition Suppresses Metastasis and Improves the Response to Immunotherapy in Pancreatic Cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr PR10.