Department of Liver Surgery, Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Department of Pediatric Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Department of Liver Surgery, Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Cell Rep Med. 2023 May 16;4(5):101044. doi: 10.1016/j.xcrm.2023.101044.
Erythroblastic islands (EBIs) are the specialized structures for erythropoiesis, but they have never been found functional in tumors. As the most common pediatric liver malignancy, hepatoblastoma (HB) requires more effective and safer therapies to prevent progression and the lifelong impact of complications on young children. However, developing such therapies is impeded by a lack of comprehensive understanding of the tumor microenvironment. By single-cell RNA sequencing of 13 treatment-naive HB patients, we discover an immune landscape characterized by aberrant accumulation of EBIs, formed by VCAM1 macrophages and erythroid cells, which is inversely correlated with survival of HB. Erythroid cells inhibit the function of dendritic cells (DCs) via the LGALS9/TIM3 axis, leading to impaired anti-tumor T cell immune responses. Encouragingly, TIM3 blockades relieve the inhibitory effect of erythroid cells on DCs. Our study provides an immune evasion mechanism mediated by intratumoral EBIs and proposes TIM3 as a promising therapeutic target for HB.
成红细胞岛（EBI）是红细胞生成的特化结构，但在肿瘤中从未发现其具有功能。作为最常见的小儿肝脏恶性肿瘤，肝母细胞瘤（HB）需要更有效和更安全的治疗方法，以防止进展和并发症对幼儿造成终身影响。然而，由于缺乏对肿瘤微环境的全面了解，此类治疗方法的开发受到了阻碍。通过对 13 名未经治疗的 HB 患者进行单细胞 RNA 测序，我们发现了一种免疫景观，其特征是 VCAM1 巨噬细胞和红细胞异常积聚形成的 EBI，这与 HB 的生存呈负相关。红细胞通过 LGALS9/TIM3 轴抑制树突状细胞（DC）的功能，导致抗肿瘤 T 细胞免疫反应受损。令人鼓舞的是，TIM3 阻断可减轻红细胞对 DC 的抑制作用。我们的研究提供了一种由肿瘤内 EBI 介导的免疫逃逸机制，并提出 TIM3 是 HB 有前途的治疗靶点。
