Cell reports. Medicine · 2023
Intratumoral erythroblastic islands restrain anti-tumor immunity in hepatoblastoma.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Wang Yuanqi, Xiang Xiao, Chen Huadong, Zhou Luyao, Chen Shuling, Zhang Guopei, Liu Xiaofei, Ren Xuxin, Liu Juncheng, Kuang Ming, Jiang Juan, She Jinbiao, Zhang Zhichong, Xue Ruidong, Jiang Hong, Wang Ji, Peng Sui
Аннотация
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.