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 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.

Treatment optimization for recurrent hepatoblastoma: retrospective study from a hepatoblastoma cohort in Southern China.

PURPOSE: The present study aimed to explore the clinical characteristics and optimal treatments of RHB patients. METHODS: We retrospectively collected 42 RHB cases and 161 primary HB (PHB) cases. Clinical characteristics were compared between RHB and PHB patients. The risk factors related to overall survival (OS) and progression-free survival (PFS) in RHB patients were explored by COX regression analysis. Patients were further divided into curable and refractory subgroup by treatments. Propensity score match (PSM) analysis was performed to match recurrent curable patients from 145 curable PHB patients from the same cohort. PFS was further compared between 34 pairs of primary and recurrent curative HB patients. RESULTS: Recurrence treatment and number of relapsed tumors were significantly related with both OS and PFS of RHB patients (p < 0.05). Chemotherapy regimen alteration was also risk factor of PFS for RHB (HR = 4.26; 95% CI = 1.54-11.78; p = 0.005). RHB patients underwent curable treatment had better prognosis, compared with recurrent refractory subgroup (p < 0.001). Matched curable PHB patients demonstrated no significant difference of 3-year PFS with curable RHB patients (p = 0.540). CONCLUSION: Curable RHB patients might get benefit from surgery or ablation with similar prognosis with primary curable HB patients.

The Prognostic Value of CD8+ and CD45RO+ T Cells Infiltration and Beclin1 Expression Levels for Early Postoperative Cholangitis of Biliary Atresia Patients after Kasai Operation.

BACKGROUND: Postoperative cholangitis is a common but severe complication after Kasai portoenterostomy for biliary atresia (BA). This study aimed to identify its prognostic factors. METHODS: Two sets of liver paraffin-embedded tissue samples were collected from BA patients who received Kasai portoenterostomy (n = 25 and n = 31, respectively). Patients were divided into non-cholangitis and cholangitis groups. The infiltration of CD4+, CD8+, CD45RO+, CD68+ cells and expression of Beclin1 were quantitatively evaluated in immunohistochemical analysis. RESULTS: Cholangitis group had a significantly lower CD8+ T cell infiltration but a higher CD45RO+ cell infiltration, and a lower Beclin1 level than non-cholangitis group (all P < 0.01). Multivariate logistic regression analysis indicated that infiltration of CD8+ cells (odds ratio [OR], 0.112; 95% confidence interval [CI], 0.022-0.577) and CD45RO+ cells (OR, 3.88; 95% CI, 1.37-11.03), and Beclin1 level (OR, 0.088; 95% CI, 0.018-0.452) were independent influence factors for early postoperative cholangitis. Receiver operating characteristic (ROC) analysis showed that area under ROC curve (AUROC) values for CD8+ cells, CD45RO+ cells and Beclin1 were 0.857, 0.738 and 0.900, respectively. CONCLUSION: Our findings demonstrated the CD8+ cells, CD45RO+ cells and Beclin1 level possessed the prognostic value for early postoperative cholangitis following Kasai operation, which may be helpful to develop new prevention and treatment strategies for postoperative cholangitis.