肿瘤相关巨噬细胞（TAM）的浸润促进胶质瘤的恶性，但其潜在机制仍不清楚。本文报告TAM分泌外泌体内源性长链非编码RNA LINC01232以诱导肿瘤免疫逃脱。从机理上讲，发现LINC01232直接结合E2F2并促进E2F2核入。两者通过协同促进NBR1的转录。NBR1结合泛素域使得NBR1与泛素化的MHC-I蛋白之间的结合增加，导致MHC-I在自噬溶酶体中降解并减少在肿瘤细胞表面的表达，从而导致肿瘤细胞逃脱CD8+CTL免疫攻击。使用shRNA干扰E2F2 / NBR1 / MHC-I信号，或使用相应的抗体阻断，可以从大量抑制LINC01232对肿瘤支持的影响，并抑制由M2型巨噬细胞驱动的肿瘤生长。重要的是，LINC01232的沉默提高了肿瘤细胞表面MHC-I的表达，并改善了对CD8+ T细胞复注的反应。本研究揭示了TAM和胶质瘤之间通过LINC01232 / E2F2 / NBR1 / MHC-I轴的关键分子相互作用的存在，支持恶性肿瘤生长，表明针对此轴的靶向治疗可能具有治疗潜力。 ©2023 Wiley-VCH GmbH出版的Advanced Science。

Tumor-associated macrophage (TAM) infiltration facilitates glioma malignancy, but the underlying mechanisms remain unclear. Herein, it is reported that TAMs secrete exosomal LINC01232 to induce tumor immune escape. Mechanistically, LINC01232 is found to directly bind E2F2 and promote E2F2 entry into the nucleus; the two synergistically promots the transcription of NBR1. The increase in binding between NBR1 binding and the ubiquitinating MHC-I protein through the ubiquitin domain causes an increase in the degradation of MHC-I in autophagolysosomes and a decrease in the expression of MHC-I on the surface of tumor cells, which in turn led to tumor cell escape from CD8+ CTL immune attack. Disruption of E2F2/NBR1/MHC-I signaling with shRNAs or blockade with the corresponding antibodies largely abolishes the tumor-supportive effects of LINC01232 and inhibits tumor growth driven by M2-type macrophages. Importantly, knockdown of LINC01232 enhances the expression of MHC-I on the surface of tumor cells and improves the response to reinfusion with CD8+ T cells. This study reveals the existence of critical molecular crosstalk between TAMs and glioma mediates through the LINC01232/E2F2/NBR1/MHC-I axis to support malignant tumor growth, indicating that targeting this axis may have therapeutic potential.© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.