Intratumoral erythroblastic islands restrain anti-tumor immunity in hepatoblastoma.
Cell Rep Med
; 4(5): 101044, 2023 05 16.
Article
en En
| MEDLINE
| ID: mdl-37196629
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Hepatoblastoma
/
Neoplasias Hepáticas
Límite:
Child
/
Child, preschool
/
Humans
Idioma:
En
Revista:
Cell Rep Med
Año:
2023
Tipo del documento:
Article
País de afiliación:
China