Intratumoral erythroblastic islands restrain anti-tumor immunity in hepatoblastoma

• DOI: 10.1016/j.xcrm.2023.101044
• Publication Date: 2023-05-16T14:36:30Z
• Authors: Yuanqi Wang; Xiao Xiang; Huadong Chen; Luyao Zhou; Shuling Chen; Guopei Zhang; Xiaofei Liu; Xuxin Ren; Juncheng Liu; Ming Kuang; Juan Jiang; Jinbiao She; Zhichong Zhang; Ruidong Xue; Hong Jiang; Ji Wang; Sui Peng
• Keywords: Hepatoblastoma

Erythroblastic islands (EBIs) are the specialized structures for erythropoiesis, but they have never been found functional in tumors. As most common pediatric liver malignancy, hepatoblastoma (HB) requires more effective and safer therapies to prevent progression lifelong impact of complications on young children. However, developing such is impeded by a lack comprehensive understanding tumor microenvironment. By single-cell RNA sequencing 13 treatment-naive HB patients, we discover an immune landscape characterized aberrant accumulation EBIs, formed VCAM1+ macrophages erythroid cells, which inversely correlated with survival HB. Erythroid cells inhibit function dendritic (DCs) via LGALS9/TIM3 axis, leading impaired anti-tumor T cell responses. Encouragingly, TIM3 blockades relieve inhibitory effect DCs. Our study provides evasion mechanism mediated intratumoral EBIs proposes as promising therapeutic target