潜入的免疫细胞引起的慢性炎症可通过激活炎症细胞因子信号通路(IL-6/p-STAT3和TNFα/NF-κB)来促进溃疡性结肠炎(UC)相关的畸形癌/结肠癌。黏膜门静脉细胞黏附分子-1(MAdCAM-1)在高内皮静脉上表达，通过与免疫细胞上表达的α4β7整合素的作用，促进免疫细胞从血液中迁移到肠道。因此，MAdCAM-1已成为治疗活动性UC的新型治疗靶点引起了关注。然而，MAdCAM-1阳性内皮细胞在畸形癌/结肠癌中的免疫细胞浸润中的作用仍不清楚。我们使用免疫组化染色，评估从11名带有畸形癌/结肠癌的UC患者和17名间断性结直肠癌患者(SCRC)中外科切除的样本中的MAdCAM-1、CD31和免疫细胞标记物(CD8、CD68、CD163和FOXP3)的表达。我们使用一种氮杂甲烷/戊糖硫酸钠小鼠模型(AOM/DSS小鼠)评估使用抗MAdCAM-1阻滞抗体是否能通过防止免疫细胞浸润来抑制畸形癌/结肠癌。在畸形癌/结肠癌中，MAdCAM-1阳性血管和浸润的CD8+、CD68+和CD163+免疫细胞的数量显著高于正常、SCRC和UC粘膜。在AOM/DSS小鼠中，抗MAdCAM-1抗体降低了肿瘤的数量、平均直径、深度，Ki67阳性率，CD8+、CD68+和CD163+免疫细胞的数量，以及IL-6/p-STAT3和TNF-α/NF-κB信号通路。我们的研究结果表明，通过调节UC患者的炎症/免疫细胞浸润，以MAdCAM-1为靶点是控制UC严重程度、癌变和肿瘤进展的有前途的策略。©2023 UICC。

Chronic inflammation caused by infiltrating immune cells can promote colitis-associated dysplasia/colitic cancer in ulcerative colitis (UC) by activating inflammatory cytokine signalling through the IL-6/p-STAT3 and TNFα/NF-κB pathways. Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) expressed on high endothelial venules promotes the migration of immune cells from the bloodstream to the gut via interaction with α4β7 integrin expressed on the immune cells. MAdCAM-1, has therefore drawn interest as a novel therapeutic target for treating active UC. However, the role of MAdCAM-1-positive endothelial cells in immune cell infiltration in dysplasia/colitic cancers remains unclear. We evaluated the expression of MAdCAM-1, CD31 and immune cell markers (CD8, CD68, CD163 and FOXP3) in samples surgically resected from 11 UC patients with dysplasia/colitic cancer and 17 patients with sporadic colorectal cancer (SCRC), using immunohistochemical staining. We used an azoxymethane/dextran sodium sulphate mouse model (AOM/DSS mouse) to evaluate whether dysplasia/colitic cancer could be suppressed with an anti-MAdCAM-1 blocking antibody by preventing immune cell infiltration. The number of MAdCAM-1-positive vessels and infiltrating CD8+ , CD68+ and CD163+ immune cells was significantly higher in dysplasia/colitic cancer than in normal, SCRC and UC mucosa. In AOM/DSS mice, the anti-MAdCAM-1 antibody reduced the number, mean diameter, depth of tumours, Ki67 positivity, number of CD8+ , CD68+ and CD163+ immune cells and the IL-6/p-STAT3 and TNF-α/NF-κB signalling. Our results indicate that targeting MAdCAM-1 is a promising strategy for controlling not only UC severity but also carcinogenesis and tumour progression by regulating inflammation/immune cell infiltration in patients with UC.© 2023 UICC.