Single-cell and spatial transcriptomics implicate a prognostic function of tertiary lymphoid structures in gastric cancer

Yanchun Wang, Guangyu Zhang, Xin Zhang, Gaoke Liu, Lihua Zhang, Lei Chen, Shuli Sang, Sheng Yao, Yang Fei, Zhichao Tian, Yu Zang, Hongwei Wang, Yiping Dong, Chunjie Liu (), Xizhao Chen (), Yan Liu () and Min Zhang ()
Additional contact information
Yanchun Wang: Beijing Institute of Biotechnology, Laboratory of Advanced Biotechnology
Guangyu Zhang: The First Affiliated Hospital of Chongqing Medical University, Department of Rheumatology and Immunology, Center for Immune Ageing and Rejuvenation
Xin Zhang: Chinese PLA General Hospital, Department of Pharmacy, Medical Supplies Center
Gaoke Liu: Army Medical University, Department of Medical Genetics, College of Basic Medical Science
Lihua Zhang: Chinese PLA General Hospital, Department of Pathology, Fourth Medical Center
Lei Chen: The First Affiliated Hospital of Xi’an Jiaotong University, Department of Critical Care Nephrology and Blood Purification
Shuli Sang: Beijing Institute of Biotechnology, Laboratory of Advanced Biotechnology
Sheng Yao: Chinese PLA General Hospital, Department of General Surgery, First Medical Center
Yang Fei: Chinese PLA General Hospital, Department of General Surgery, First Medical Center
Zhichao Tian: Chinese PLA General Hospital, Department of General Surgery, First Medical Center
Yu Zang: Chinese PLA General Hospital, Department of Pathology, Fourth Medical Center
Hongwei Wang: Chinese PLA General Hospital, Department of Pathology, Fourth Medical Center
Yiping Dong: Army Medical University, Department of Medical Genetics, College of Basic Medical Science
Chunjie Liu: Beijing Institute of Biotechnology, Laboratory of Advanced Biotechnology
Xizhao Chen: Chinese PLA General Hospital, Department of Nephrology, First Medical Center
Yan Liu: Chinese PLA General Hospital, Department of Gastroenterology, First Medical Center
Min Zhang: Chinese PLA General Hospital, Department of Nephrology, First Medical Center

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract Tertiary lymphoid structures (TLSs) have emerged as critical prognostic and immunotherapeutic indicators in cancer, with their clinical significance modulated by spatial distribution patterns and density. Here, we performed integrated single-cell and spatial transcriptomic profiling of 30 gastric cancer (GC) specimens stratified by TLS spatial localization patterns. Comparative analysis shows pronounced enrichment of CXCL13+ T lymphocytes (TLCs), CXCR5+ germinal center B lymphocytes (gc_B cells), LAMP3+CD80+ activated dendritic cells (DCs), and SELP+ACKR1+ high endothelial venule (HEV) cells within intratumoral-TLS (iTLS) rich tumors compared to peritumoral-TLS (pTLS) and desert-TLS (dTLS) tumor subtypes. Multimodal cell–cell interaction analysis and functional experiments demonstrate that HEV expressed VCAM1 and ICAM1 recruits and activates CXCL13+ TLC through the CXCL13-ACKR1 pathway, which promotes TLS formation via CXCL13-CXCR5-dependent crosstalk with B lymphocytes. We further develop a single-cell/spatial TLS signature that captures the cellular ecosystem of iTLS-containing tumor, demonstrating predictive value for immunotherapy outcomes in GC patients.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-65421-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-65421-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-65421-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().