Intratumoral erythroblastic islands restrain anti-tumor immunity in hepatoblastoma

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 chil-dren. However, developing such therapies is impeded by a lack of comprehensive understanding of the tu-mor microenvironment. By single-cell RNA sequencing of 13 treatment-naive HB patients, we discover an im-mune 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. Encourag-ingly, 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.

Automated summary

By analyzing single-cell RNA sequencing data from 13 treatment-naive hepatoblastoma patients, researchers discovered the presence of aberrant accumulation of erythroblastic islands (EBIs), which are formed by VCAM1+ macrophages and erythroid cells, in the tumor microenvironment. This phenomenon is inversely correlated with the survival of hepatoblastoma. Erythroid cells inhibit the function of dendritic cells through the LGALS9/TIM3 axis, leading to impaired anti-tumor T cell immune responses. Blocking TIM3 can relieve the inhibitory effect of erythroid cells on dendritic cells.