The endothelial cell–neutrophil axis: Mechanisms and therapeutic perspectives in colitis-associated carcinogenesis

Endothelial dysfunction coupled with neutrophil infiltration drives colitis-associated carcinogenesis (CAC). Vascular endothelial cells sustain homeostasis and immune surveillance. In CAC, endothelial impairment increases vascular permeability, recruits neutrophils, aggravates inflammation, and further stimulates angiogenesis, thereby promoting tumor proliferation and metastasis. Targeting endothelial signaling cascades, including the VEGF and MAPK axes, represents a promising strategy for suppressing inflammatory responses and tumor outgrowth. Blockade of adhesion molecules such as VCAM-1 and ICAM-1 curtails neutrophil recruitment and mitigates intestinal inflammatory lesions. Anti-VEGF and MAPK-targeted interventions have been investigated in cancer and inflammatory diseases, and emerging work on neutrophil extracellular traps opens new therapeutic directions. Despite these mechanistic and translational advances, a systematic overview of the interplay between endothelial cells and neutrophils during CAC remains lacking. Here we describe the central contribution of endothelial dysfunction to the multistep progression of CAC, discuss how therapeutic modulation of the endothelial cell-neutrophil axis could optimize clinical outcomes, and highlight vascular endothelium-targeted interventions as promising strategies for limiting CAC progression.