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儿童 Group 4 髓母细胞瘤中肿瘤浸润 B 细胞的富集

英文原题:Enrichment of Tumor-Infiltrating B Cells in Group 4 Medulloblastoma in Children.

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Enrichment of Tumor-Infiltrating B Cells in Group 4 Medulloblastoma in Children.

PubMed 2022/05/09(内容时间) Int J Mol Sci Q1 · IF 5.6(JCR 2025)

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中文摘要

髓母细胞瘤(MB)是儿童最常见的恶性脑肿瘤,分为几个核心分子亚组:WNT通路激活型、SHH通路激活型、第3组(G3)和第4组(G4)。

本研究利用转录组数据,分析台湾70例MB患者的肿瘤浸润免疫细胞和细胞因子谱;同时分析SickKids队列数据集中肿瘤的免疫细胞组成,以验证结果。临床队列数据显示,在四个亚组中,WNT和G4患者复发率较低,5年无复发生存率(RFP)优于SHH和G3患者。

研究发现,台湾患者及SickKids队列的G4亚组均富集肿瘤浸润B细胞(TIL-B)。G4亚组中,TIL-B水平较高的患者5年总生存率更好。G4 MB肿瘤中的肥大细胞与TIL-B呈正相关。与其他亚组或正常脑组织相比,G4中CXCL13、IL-36和CCL27水平较高。这三种细胞因子、B细胞和肥大细胞共同构成G4 MB独特的免疫微环境。

因此,B细胞富集是G4亚组特异性免疫特征,B细胞存在可能预示G4 MB患者预后较好。

展开英文摘要原文

Medulloblastoma (MB) is the most common malignant brain tumor in children. It is classified into core molecular subgroups (wingless activated (WNT), sonic hedgehog activated (SHH), Group 3 (G3), and Group 4 (G4)). In this study, we analyzed the tumor-infiltrating immune cells and cytokine profiles of 70 MB patients in Taiwan using transcriptome data.

In parallel, immune cell composition in tumors from the SickKids cohort dataset was also analyzed to confirm the findings. The clinical cohort data showed the WNT and G4 MB patients had lower recurrence rates and better 5-year relapse-free survival (RFP) compared with the SHH and G3 MB patients, among the four subgroups of MB.

We found tumor-infiltrating B cells (TIL-Bs) enriched in the G4 subgroups in the Taiwanese MB patients and the SickKids cohort dataset. In the G4 subgroups, the patients with a high level of TIL-Bs had better 5-year overall survival. Mast cells presented in G4 MB tumors were positively correlated with TIL-Bs. Higher levels of CXCL13, IL-36 , and CCL27 were found compared to other subgroups or normal brains. These three cytokines, B cells and mast cells contributed to the unique immune microenvironment in G4 MB tumors.

Therefore, B-cell enrichment is a G4-subgroup-specific immune signature and the presence of B cells may be an indicator of a better prognosis in G4 MB patients.

论文信息

作者
Wu KS、Jian TY、Sung SY、Hsieh CL、Huang MH、Fang CL、Wong TT、Lin YL
第一作者单位
Graduate Institute of Clinical Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.Taiwan
通讯作者单位
Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan.Taiwan
期刊
International journal of molecular sciences2022 May 9
原文标识
PubMed 35563678 · DOI 10.3390/ijms23095287