近日，美国吉尔·罗伯茨炎症性肠病研究所教授Randy S. Longman及其课题组的论文发现了由细胞因子TL1A激活的先天淋巴样细胞将结肠炎与紧急粒细胞生成和促肿瘤中性粒细胞的募集联系起来。该研究于2026年1月22日发表于国际一流学术期刊《免疫学》杂志上。

该研究团队研究了TL1A信号如何促进结肠炎相关的肿瘤发生。组织驻留型3先天淋巴样细胞（ILC3s）中TL1A受体的缺失减少了结肠炎相关的肿瘤发生。TL1A信号传导促进中性粒细胞向结肠募集，这是肿瘤发展所必需的。TL1A刺激的ILC3s激活中性粒细胞，诱导肿瘤相关的中性粒细胞（TAN）样基因标记，这些中性粒细胞的转移足以促进肿瘤生长。类似的TAN样基因标记在人类结肠炎相关的发育不良中丰富，但在溃疡性结肠炎患者中TL1A阻断后减少。在机制上，TL1A和结肠炎触发紧急粒细胞生成，以依赖于ILC3s衍生的粒细胞-巨噬细胞集落刺激因子（GM-CSF）的方式扩大粒细胞-单核细胞祖细胞和中性粒细胞。因此，TL1A-ILC3-GM-CSF轴将结肠炎与紧急颗粒生成联系起来，并可能作为减少结肠炎相关CRC的治疗靶点。

研究人员表示，炎症性肠病（IBD）增加结直肠癌（CRC）的风险。编码肿瘤坏死因子（TNF）样细胞因子1A （TL1A）的TNFSF15基因变异与严重IBD和晚期CRC相关。

附：英文原文

Title: Innate lymphoid cells activated by the cytokine TL1A link colitis to emergency granulopoiesis and the recruitment of tumor-promoting neutrophils

Author: Sílvia Pires, Wei Yang, Sofia Frigerio, Cynthia Louis, Chloe Scott, Yu Lin Zhou, Emre Cardakli, Nancy Tran, Mina Hassan-Zahraee, Zhan Ye, Craig Hyde, Kenneth Hung, Amanda Chen, Charles Ng, Alexander Grier, Dana Lukin, Ellen Scherl, Stephan R. Targan, Gretchen E. Diehl, Joep Grootjans, Tracy L. Putoczki, Ian Wicks, Randy S. Longman

Issue&Volume: 2026-01-22

Abstract: Inflammatory bowel disease (IBD) increases the risk of colorectal cancer (CRC). Genetic variants in TNFSF15, encoding tumor necrosis factor (TNF)-like cytokine 1A (TL1A), associate with severe IBD and advanced CRC. Here, we investigated how TL1A signaling promotes colitis-associated tumorigenesis. Deletion of the TL1A receptor in tissue-resident type 3 innate lymphoid cells (ILC3s) reduced colitis-associated tumorigenesis. TL1A signaling promoted neutrophil recruitment to the colon, which was required for tumor development. TL1A-stimulated ILC3s activated neutrophils, inducing a tumor-associated neutrophil (TAN)-like gene signature, and transfer of these neutrophils was sufficient to promote tumor growth. A similar TAN-like gene signature was enriched in human colitis-associated dysplasia but reduced following TL1A blockade in ulcerative colitis patients. Mechanistically, TL1A and colitis triggered emergency granulopoiesis, expanding granulocyte-monocyte progenitors and neutrophils in a manner dependent on ILC3-derived granulocyte-macrophage colony-stimulating factor (GM-CSF). Thus, a TL1A-ILC3-GM-CSF axis links colitis with emergency granulopoiesis and may serve as a therapeutic target to reduce colitis-associated CRC.

DOI: 10.1016/j.immuni.2025.12.008

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00564-3