Frontiers in Immunology (Jul 2024)
The distribution and maturation of tertiary lymphoid structures can predict clinical outcomes of patients with gastric adenocarcinoma
- Hui Sun,
- Hui Sun,
- Hui Sun,
- Yuxi Liu,
- Yuxi Liu,
- Yuxi Liu,
- Wanjing Cheng,
- Wanjing Cheng,
- Wanjing Cheng,
- Rong Xiong,
- Rong Xiong,
- Rong Xiong,
- Wenchao Gu,
- Xiaoyan Zhang,
- Xiaoyan Zhang,
- Xiaoyan Zhang,
- Xin Wang,
- Xin Wang,
- Xin Wang,
- Xu Wang,
- Xu Wang,
- Xu Wang,
- Cong Tan,
- Cong Tan,
- Cong Tan,
- Weiwei Weng,
- Weiwei Weng,
- Weiwei Weng,
- Meng Zhang,
- Meng Zhang,
- Meng Zhang,
- Shujuan Ni,
- Shujuan Ni,
- Shujuan Ni,
- Dan Huang,
- Dan Huang,
- Dan Huang,
- Midie Xu,
- Midie Xu,
- Midie Xu,
- Weiqi Sheng,
- Weiqi Sheng,
- Weiqi Sheng,
- Lei Wang,
- Lei Wang,
- Lei Wang
Affiliations
- Hui Sun
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Hui Sun
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Hui Sun
- Institute of Pathology, Fudan University, Shanghai, China
- Yuxi Liu
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Yuxi Liu
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Yuxi Liu
- Institute of Pathology, Fudan University, Shanghai, China
- Wanjing Cheng
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Wanjing Cheng
- Pathology Department of HaiNan General Hospital, HaiNan, China
- Wanjing Cheng
- Department of Diagnostic and Interventional Radiology, University of Tsukuba, Tsukuba, Japan
- Rong Xiong
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Rong Xiong
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Rong Xiong
- Institute of Pathology, Fudan University, Shanghai, China
- Wenchao Gu
- Department of Diagnostic and Interventional Radiology, University of Tsukuba, Tsukuba, Japan
- Xiaoyan Zhang
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Xiaoyan Zhang
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Xiaoyan Zhang
- Institute of Pathology, Fudan University, Shanghai, China
- Xin Wang
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Xin Wang
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Xin Wang
- Institute of Pathology, Fudan University, Shanghai, China
- Xu Wang
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Xu Wang
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Xu Wang
- Institute of Pathology, Fudan University, Shanghai, China
- Cong Tan
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Cong Tan
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Cong Tan
- Institute of Pathology, Fudan University, Shanghai, China
- Weiwei Weng
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Weiwei Weng
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Weiwei Weng
- Institute of Pathology, Fudan University, Shanghai, China
- Meng Zhang
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Meng Zhang
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Meng Zhang
- Institute of Pathology, Fudan University, Shanghai, China
- Shujuan Ni
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Shujuan Ni
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shujuan Ni
- Institute of Pathology, Fudan University, Shanghai, China
- Dan Huang
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Dan Huang
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Dan Huang
- Institute of Pathology, Fudan University, Shanghai, China
- Midie Xu
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Midie Xu
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Midie Xu
- Institute of Pathology, Fudan University, Shanghai, China
- Weiqi Sheng
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Weiqi Sheng
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Weiqi Sheng
- Institute of Pathology, Fudan University, Shanghai, China
- Lei Wang
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Lei Wang
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Lei Wang
- Institute of Pathology, Fudan University, Shanghai, China
- DOI
- https://doi.org/10.3389/fimmu.2024.1396808
- Journal volume & issue
-
Vol. 15
Abstract
IntroductionTertiary 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.MethodsThus, 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.ResultsWe 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.DiscussionOur 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.
Keywords
- stomach adenocarcinoma
- tertiary lymphoid structure (TLS)
- distribution of TLSs
- maturation of TLSs
- DC-LAMP+ dendritic cells
- prognosis
