文章：

APOE缺乏可激发巨噬细胞在肝癌中的抗肿瘤活性

APOE deficiency triggers anti-tumour activity of macrophages in liver cancer 

原文发布日期：2025-07-14 

英文摘要：

Macrophage infiltration correlates with poor prognosis in patients with liver cancer and resistance to immunotherapy. However, it is difficult to target tumour-associated macrophages (TAMs) because of their inherent heterogeneity. Specific TAM subsets may exhibit distinct functions in tumorigenesis. Herein, we identify a TAM subset characterised by elevated APOE expression, which is correlated with poor overall survival of patients with HCC. The APOE+ TAM intensity is highly elevated in ICB non-responder tumours and negatively correlated with CD8+ T cell infiltration. Pathway analysis and cell interaction reveal that APOE+ TAMs suppress CD8+ T cells through signal integration and cholesterol efflux. Furthermore, APOE deficiency in macrophages delays tumour growth and promotes the infiltration of CD8+ T cells. Using an immunotherapy-resistant mouse model, we showed that APOE blockade synergises with anti-PD-1 therapy and inhibits tumour growth. Our results elucidate the crucial role of APOE+ TAMs in the formation of immunosuppressive microenvironments and offer a potential therapeutic target for ICB combined therapy. 

摘要翻译：

巨噬细胞浸润与肝癌患者不良预后及免疫治疗耐药性相关。然而，由于肿瘤相关巨噬细胞（TAMs）固有的异质性，靶向治疗一直面临挑战。特定TAM亚群在肿瘤发生过程中可能表现出截然不同的功能。本研究识别出一种以APOE高表达为特征的TAM亚群，该亚群与肝细胞癌（HCC）患者总生存期缩短显著相关。在免疫检查点阻断（ICB）无应答肿瘤中，APOE+ TAM密度显著升高，且与CD8+ T细胞浸润呈负相关。通路分析和细胞互作研究表明，APOE+ TAM通过信号整合和胆固醇外流机制抑制CD8+ T细胞功能。此外，巨噬细胞中APOE的缺失可延缓肿瘤生长并促进CD8+ T细胞浸润。利用免疫治疗耐药小鼠模型，我们发现阻断APOE与抗PD-1疗法具有协同作用，能有效抑制肿瘤生长。本研究阐明了APOE+ TAM在免疫抑制微环境形成中的关键作用，为ICB联合治疗提供了潜在靶点。

原文链接：

APOE deficiency triggers anti-tumour activity of macrophages in liver cancer