Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Front Immunol. 2024 Jul 29;15:1396808. doi: 10.3389/fimmu.2024.1396808. eCollection 2024.
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.
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.
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.
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.
三级淋巴结构（TLSs）是类似于次级淋巴器官的结构，其中包含各种免疫细胞。TLSs 的空间分布、成熟和组成对预后有不同的影响，而其在胃腺癌（GA）中的作用尚未被揭示。
因此，我们通过分析公共数据库中的批量 RNA 测序（RNA-seq）数据，评估了 TLSs 在 GA 中的预后价值，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。通过复习 H&E 染色切片和多重免疫荧光（mIF）染色，分析了 GA 中 TLSs 的空间分布、成熟和组成。
我们发现，TLSs，特别是具有生发中心（GCs）的 TLSs 和位于浸润前缘（IM）的 TLSs，与延长的总生存期（OS）相关。其次，公共 RNA-seq 数据分析显示，高树突状细胞（DC）评分是 GA 患者的有利预后因素，这些患者的 TLSs 和 GCs 评分均较高。在 FUSCC 队列中，在具有 GCs 的 IM-TLSs 中，DC-LAMP+DCs 明显富集，表明肿瘤免疫激活环境与 DC 丰度之间可能存在相关性。第三，与无 GCs 的 TLSs 相比，具有 GCs 的 IM-TLSs 中 FOXP3+CD8+Treg 细胞的比例明显降低，而 GCs 中 PD1+CD20+B 细胞的百分比明显增加。
我们的结果表明，TLSs 的空间排列和成熟度对预后有显著影响，并表明 TLSs 可能是组织病理学评估的一个新的附加因素。
