海军军医大学袁继行等研究人员合作发现，ERMAP、galectin-9和dectin-2之间的结合可促进库普弗细胞的吞噬能力和抗肿瘤免疫力。这一研究成果于2023年10月9日在线发表在国际学术期刊《自然—免疫学》上。

通过体内全基因组CRISPR-Cas9基因敲除筛选，研究人员发现在各种癌细胞上表达的细胞表面跨膜蛋白ERMAP是激活库普弗细胞吞噬功能和控制肝转移的信号。ERMAP与库普弗细胞表面表达的β-半乳糖苷结合凝集素galectin-9相互作用，其方式依赖于糖基化。

galectin-9与ERMAP和库普弗细胞上表达的跨膜受体dectin-2形成桥接复合物，然后诱导库普弗细胞检测和吞噬癌细胞。肿瘤上ERMAP表达量低的患者发生肝转移的几率更高。因此，这项研究确定ERMAP-galectin-9-dectin-2轴是库普弗细胞“吃我”的信号。

研究人员表示，库普弗细胞是肝脏组织中的常驻巨噬细胞，对检测和清除癌细胞至关重要。然而，它们检测和吞噬癌细胞的分子机制仍不清楚。

附：英文原文

Title: The ligation between ERMAP, galectin-9 and dectin-2 promotes Kupffer cell phagocytosis and antitumor immunity

Author: Li, Jie, Liu, Xiao-gang, Ge, Rui-liang, Yin, Yu-peng, Liu, Yong-da, Lu, Wan-peng, Huang, Mei, He, Xue-ying, Wang, Jinghan, Cai, Guoxiang, Sun, Shu-han, Yuan, Ji-hang

Issue&Volume: 2023-10-09

Abstract: Kupffer cells, the liver tissue resident macrophages, are critical in the detection and clearance of cancer cells. However, the molecular mechanisms underlying their detection and phagocytosis of cancer cells are still unclear. Using in vivo genome-wide CRISPR-Cas9 knockout screening, we found that the cell-surface transmembrane protein ERMAP expressed on various cancer cells signaled to activate phagocytosis in Kupffer cells and to control of liver metastasis. ERMAP interacted with β-galactoside binding lectin galectin-9 expressed on the surface of Kupffer cells in a manner dependent on glycosylation. Galectin-9 formed a bridging complex with ERMAP and the transmembrane receptor dectin-2, expressed on Kupffer cells, to induce the detection and phagocytosis of cancer cells by Kupffer cells. Patients with low expression of ERMAP on tumors had more liver metastases. Thus, our study identified the ERMAP–galectin–9-dectin-2 axis as an ‘eat me’ signal for Kupffer cells.

DOI: 10.1038/s41590-023-01634-7

Source: https://www.nature.com/articles/s41590-023-01634-7