PDF(Pubmed)
Abstract：
UNASSIGNED: Tertiary lymphoid structures (TLSs) are analogues of secondary lymphoid organs that contain various immune cells. The spatial distribution, maturation and composition of TLSs have differential effects on prognosis, and the roles of TLSs in gastric adenocarcinoma (GA) have not been revealed.
UNASSIGNED: Thus, we evaluated the prognostic value of TLSs in GA through analysis of bulk RNA sequencing(RNA-seq) data from public databases and validated our findings in tumour samples from the Fudan University Shanghai Cancer Center (FUSCC) cohort. The spatial distribution,maturation, and composition of TLSs in GA were analysed by reviewing H&E-stained sections and by multiplex immunofluorescence (mIF) staining.
UNASSIGNED: We found that TLSs, especially TLSs with germinal centres (GCs) and TLSs located in the invasive margin (IM), were correlated with prolonged overall survival (OS). Second, analysis of public RNA-seq data showed that high dendritic cell (DC) scores were a favourable prognostic factor in GA patients with high scores for both TLSs and GCs. In the FUSCC cohort, DC-LAMP+ DCs weresignificantly enriched in IM-TLSs with GCs, suggesting a potential correlation between the tumour immune activation milieu and the DC abundance. Third, compared to that in TLSs without GCs, the proportion of FOXP3+CD8+ Treg cells was significantly decreased in IM-TLSs with GCs, and the percentage of PD1+CD20+ B cells was significantly increased in TLSs with GCs.
UNASSIGNED: Our results demonstrate that the spatial arrangement and maturation of TLSs significantly affect prognosis and indicate that TLSs could be a new additional factor for histopathological evaluation.
UNASSIGNED: Thus, we evaluated the prognostic value of TLSs in GA through analysis of bulk RNA sequencing(RNA-seq) data from public databases and validated our findings in tumour samples from the Fudan University Shanghai Cancer Center (FUSCC) cohort. The spatial distribution,maturation, and composition of TLSs in GA were analysed by reviewing H&E-stained sections and by multiplex immunofluorescence (mIF) staining.
UNASSIGNED: We found that TLSs, especially TLSs with germinal centres (GCs) and TLSs located in the invasive margin (IM), were correlated with prolonged overall survival (OS). Second, analysis of public RNA-seq data showed that high dendritic cell (DC) scores were a favourable prognostic factor in GA patients with high scores for both TLSs and GCs. In the FUSCC cohort, DC-LAMP+ DCs weresignificantly enriched in IM-TLSs with GCs, suggesting a potential correlation between the tumour immune activation milieu and the DC abundance. Third, compared to that in TLSs without GCs, the proportion of FOXP3+CD8+ Treg cells was significantly decreased in IM-TLSs with GCs, and the percentage of PD1+CD20+ B cells was significantly increased in TLSs with GCs.
UNASSIGNED: Our results demonstrate that the spatial arrangement and maturation of TLSs significantly affect prognosis and indicate that TLSs could be a new additional factor for histopathological evaluation.
摘要：
■三级淋巴结构（TLSs）是包含各种免疫细胞的二级淋巴器官的类似物。空间分布,TLS的成熟和组成对预后有不同的影响，TLS在胃腺癌（GA）中的作用尚未揭示。
■因此，我们通过分析来自公共数据库的大量RNA测序(RNA-seq)数据,评估了GA中TLS的预后价值,并在复旦大学上海癌症中心(FUSCC)队列的肿瘤样本中验证了我们的发现.空间分布,成熟,通过回顾H＆E染色的切片和多重免疫荧光（mIF）染色来分析GA中TLS的组成。
■我们发现TLS，尤其是具有生发中心（GC）的TLS和位于侵入性边缘（IM）的TLS，与总生存期（OS）延长相关。第二,对公开RNA-seq数据的分析显示，高树突状细胞（DC）评分是TLS和GC评分高的GA患者的有利预后因素。在FUSCC队列中，DC-LAMP+DC在具有GC的IM-TLSs中显著富集，表明肿瘤免疫激活环境与DC丰度之间存在潜在的相关性。第三，与没有GC的TLS相比，IM-TLSs中FOXP3+CD8+Treg细胞的比例显著降低，PD1+CD20+B细胞的比例显著增加。
■我们的结果表明，TLS的空间排列和成熟显着影响预后，并表明TLS可能是组织病理学评估的新附加因素。
■因此，我们通过分析来自公共数据库的大量RNA测序(RNA-seq)数据,评估了GA中TLS的预后价值,并在复旦大学上海癌症中心(FUSCC)队列的肿瘤样本中验证了我们的发现.空间分布,成熟,通过回顾H＆E染色的切片和多重免疫荧光（mIF）染色来分析GA中TLS的组成。
■我们发现TLS，尤其是具有生发中心（GC）的TLS和位于侵入性边缘（IM）的TLS，与总生存期（OS）延长相关。第二,对公开RNA-seq数据的分析显示，高树突状细胞（DC）评分是TLS和GC评分高的GA患者的有利预后因素。在FUSCC队列中，DC-LAMP+DC在具有GC的IM-TLSs中显著富集，表明肿瘤免疫激活环境与DC丰度之间存在潜在的相关性。第三，与没有GC的TLS相比，IM-TLSs中FOXP3+CD8+Treg细胞的比例显著降低，PD1+CD20+B细胞的比例显著增加。
■我们的结果表明，TLS的空间排列和成熟显着影响预后，并表明TLS可能是组织病理学评估的新附加因素。
