Tumor-associated macrophages (TAM), which are found in the tumor microenvironment of solid tumors, not only mediate cancer immune evasion but also promote tumor growth. The transcription factor NF-κB, which is a crucial link between inflammation and tumors, can accelerate tumor occurrence and development. NEMO, the regulatory subunit of the IKK complex, plays a pivotal role in activating the NF-κB signaling pathway. However, the function of myeloid NEMO in the tumor microenvironment remains unclear. Here, we found that conditional knockout of NEMO in myeloid cells promoted tumor growth in a transplanted cancer mouse model. In Nemo^fl/fl lyz-cre^+/- mice, the deletion of Nemo in myeloid cells increased the recruitment of M2 macrophages and myeloid-derived suppressor cells (MDSCs) into the tumor, reduced the expression of apoptosis-related proteins, and upregulated the expression of the chemokine receptor CCR2, thereby promoting tumor growth in vivo. Then, we showed that blocking the MCP1-CCR2 pathway could inhibit tumor growth, especially in mice with myeloid NEMO deletion. In this study, we examined the mechanism of NEMO in myeloid cells and explored the role of NEMO in the prevention and treatment of cancer.

在实体瘤的肿瘤微环境中发现的肿瘤相关巨噬细胞（TAM），不仅介导癌症的免疫逃避，而且还促进了肿瘤的生长。转录因子NF-κB是炎症与肿瘤之间的重要纽带，可加速肿瘤的发生和发展。NEMO是IKK复合物的调节亚基，在激活NF-κB信号通路中起关键作用。但是，骨髓NEMO在肿瘤微环境中的功能仍不清楚。在这里，我们发现有条件的敲除骨髓细胞NEMO促进了移植的癌症小鼠模型中的肿瘤生长。在Nemo ^{fl / fl} lyz-cre ^+/-小鼠，髓细胞中Nemo的缺失增加了M2巨噬细胞和髓源性抑制细胞（MDSC）向肿瘤中的募集，减少了凋亡相关蛋白的表达，并上调了趋化因子受体CCR2的表达，从而促进了肿瘤体内生长。然后，我们证明了阻断MCP1-CCR2通路可以抑制肿瘤的生长，尤其是在具有髓样NEMO缺失的小鼠中。在这项研究中，我们检查了NEMO在髓样细胞中的机制，并探讨了NEMO在预防和治疗癌症中的作用。