Single-cell analyses reveal lymph node-tumor ecosystem remodeling during lymph node metastasis of gastric cancer.

Authors

Zhi Zheng, Yuxi Zhang, Zimeng Wang, Bihan Liu, Yuankang Yang, Lehan Pan, Chenglin Xin, Tianzhen Zhang, Rui Xu, Danqing Zhu, Zhongtao Zhang, Yingchi Yang, Jun Zhang, Dan Tian

Published in

Cell reports. Volume 45. Issue 10. Pages 118147. Oct 15, 2026. Epub Oct 15, 2026.

Abstract

Gastric cancer (GC) is a highly aggressive malignancy with a strong propensity for lymph node metastasis. To characterize the metastatic ecosystem, we perform integrated single-cell transcriptomic and T cell receptor profiling of 156,871 cells from 30 primary tumors and matched sentinel lymph nodes (SLNs), spanning non-metastatic and metastatic tumors and SLNs from non-metastatic to micro- and macro-metastatic states. We identify LN-enriched progenitor exhausted T cells as a potential reservoir for tumor-infiltrating exhausted CD8⁺ T cells and reveal dynamic remodeling of the lymph node microenvironment by tumor-associated macrophages during disease progression. We further show that ILC3s promote a pro-metastatic microenvironment in micro-metastatic lymph nodes through the AREG-EGFR axis, facilitating lymphatic dissemination and subsequent establishment of CD24⁺ tumor cells. Collectively, these findings provide a stage-resolved view of the tumor-lymph node metastatic ecosystem and identify potential therapeutic targets in GC.

PMID:
42886559
Bibliographic data and abstract were imported from PubMed on 17 Oct 2026.

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