鼻咽癌（NPC）是头颈部上皮来源的恶性肿瘤，在华南、东南亚和北非地区发病率较高。肿瘤相关巨噬细胞（Mφs）（TAM）介导的免疫抑制干预是对抗肿瘤转移的潜在治疗策略，但TAM介导的鼻咽癌免疫抑制的确切机制尚不清楚。此外，TAM如何通过代谢影响鼻咽癌的发生、发展也鲜有涉及。在这项工作中，我们发现 NPC 细胞促进 M2 型 Mφ 极化并增加衣康酸 (ITA) 的释放。此外，TAM 通过免疫反应基因 1 (IRG1) 催化 ITA 的产生，促进 NPC 细胞增殖、迁移和侵袭。然后，IRG1介导的TAM中ITA的产生抑制了CD8 T细胞的杀伤，诱导TAM的M2型极化，并减少TAM的吞噬作用。此外，我们证明 ITA 通过结合和抑制 10-11 易位-2 (TET2) 表达发挥肿瘤免疫抑制作用。最后，我们证明ITA通过促进CD34造血干细胞人源化小鼠的免疫逃逸来促进NPC生长。总之，TAM 衍生的 ITA 通过靶向 TET2 增强免疫逃逸，从而促进了 NPC 进展，强调干扰 ITA 的代谢途径可能是 NPC 治疗的潜在策略。© 2024。作者。

Nasopharyngeal carcinoma (NPC) is a malignant tumor of epithelial origin in head and neck with high incidence rate in South China, Southeast Asia and North Africa. The intervention of tumor-associated macrophages (Mφs) (TAMs)-mediated immunosuppression is a potential therapeutic strategy against tumor metastasis, but the exact mechanisms of TAM-mediated immunosuppression in nasopharyngeal carcinoma are unclear. Furthermore, how TAM affects the occurrence and development of nasopharyngeal carcinoma through metabolism is rarely involved. In this work, we revealed that NPC cells promoted M2-type Mφ polarization and elevated itaconic acid (ITA) release. Also, TAMs facilitated NPC cell proliferation, migration, and invasion through immune response gene 1 (IRG1)-catalyzed ITA production. Then, IRG1-mediated ITA production in TAMs repressed the killing of CD8+ T cells, induced M2-type polarization of TAMs, and reduced the phagocytosis of TAMs. Moreover, we demonstrated ITA played a tumor immunosuppressive role by binding and dampening ten-eleven translocation-2 (TET2) expression. Finally, we proved that ITA promotes NPC growth by facilitating immune escape in CD34+ hematopoietic stem cell humanized mice. In Conclusion, TAM-derived ITA facilitated NPC progression by enhancing immune escape through targeting TET2, highlighting that interfering with the metabolic pathway of ITA may be a potential strategy for NPC treatment.© 2024. The Author(s).