Work

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

Year: 2025

Type: article

Abstract: The tertiary lymphoid structure (TLS) served as prognostic and immunotherapeutic indicator in cancer, influenced by its spatial distribution and density. Herein, we implemented TCR, single-cell, and spatial sequencing to elucidate the tumor microenvironment (TME) complexity in 25 gastric cancer (GC) samples with varying TLS distributions. We observed significant accumulation of CXCL13 + CD103 + T lymphocyte cell (TLC), CXCR5 + germinal center B lymphocyte cell (BLC), LAMP3 + dendritic cell (DC), SELP + high endothelial venule (HEV), CXCL12 + matrix cancer associated fibroblast (mCAF) and CXCL16 + tumor cell in intratumor TLS (iTLS) GC compared to peritumor TLS (pTLS) and desert TLS (dTLS). Intercellular crosstalk unveiled CXCL16 + tumor cells, CXCL12 + mCAFs, and SELP + HEVs mediate the recruitment of CXCL13 + TLCs through the CXCL16-CXCR6 and CXCL12-CXCR4 pathways, generating CXCR5 + BLCs recruitment via the CXCL13-CXCR5 pathway, indicative of GC TLS formation mechanism. Lastly, we proposed inflammatory TLS (iTLS) signature with cellular features within iTLS-GC TME, predicting GC immunotherapy prognosis.

Source: Nature Communications

DOI: 10.1038/s41467-025-65421-8