Figure 1.

The schematic summarizes polymorphonuclear leukocyte (PMN) recruitment mechanisms in inflamed colon mucosa and colon cancer, highlighting the requirement of transendothelial migration (TEM) portal formation, involving vessel-associated macrophage (VAM) and pericyte signaling, enrichment of adhesion molecules intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), and establishment of chemokine gradients. As PMNs cross the blood vessels and enter tissues, they undergo niche-specific reprogramming, acquiring diverse functional phenotypes, resulting in beneficial or detrimental impacts on disease outcomes. Most protective and detrimental PMN effector functions are enacted via the release of either proresolution or cytotoxic factors, as summarized above. Finally, potential therapeutic approaches currently under investigation or in various testing phases, including inhibition of PMN chemokine receptors or secreted damaging factors, have been discussed. CRC, colorectal cancer; CXCR2, C-X-C chemokine receptor 2; DC, dendritic cell; DSB, double-stranded break; ECM, extracellular matrix; H₂O₂, hydrogen peroxide; IBD, inflammatory bowel disease; MDSC, myeloid-derived suppressor cell; MMP, matrix metalloproteinase; MPO, myeloperoxidase; NET, neutrophil extracellular trap; NK, natural killer; ROS, reactive oxygen species; TGF-1β, transforming growth factor-1β; VEGF, vascular endothelial growth factor.