Pancreatic Cancer: Planning Ahead for Metastatic Spread Ingunn M. Stromnes, Philip D. Greenberg  Cancer Cell  Volume 29, Issue 6, Pages 774-776 (June 2016) DOI: 10.1016/j.ccell.2016.05.013 Copyright © 2016 Terms and Conditions

Figure 1 CXCR2 Signaling and Neutrophils Are Required for Metastasis Formation and Promote Adaptive Immune Resistance in a Genetically Engineered Mouse Model of PDA (A) CXCR2 signaling and neutrophils promote metastasis. Both cancer cells and cancer-associated fibroblasts produce CXCR2 ligands in pancreatic cancer. CXCR2 signaling in neutrophils promotes extracellular matrix (ECM) deposition and inhibits both T cell and macrophage accumulation in primary tumors. In distant normal tissues potentially at the pre-metastatic stage, CXCR2 signaling instead increases both neutrophil and macrophage accumulation, indicating tissue-specific effects of CXCR2 signaling. Metastases only develop when neutrophils or CXCR2 signaling are present, suggesting that neutrophils promote tumor cell exit from the primary tumor and/or cancer cell colonization of distant organs. (B) Blockade of CXCR2 or depleting neutrophils inhibits metastasis. Disrupting CXCR2 signaling or depleting neutrophils prevents spontaneous metastasis formation, which is associated with an increase in T cell and macrophage accumulation in primary tumors and a concurrent loss of ECM. Blockade of CXCR2 in combination with anti-PD1 prolongs survival in a small subset of mice with advanced PDA and thus can overcome one mechanism of adaptive immune resistance in solid tumors. Cancer Cell 2016 29, 774-776DOI: (10.1016/j.ccell.2016.05.013) Copyright © 2016 Terms and Conditions