A spatially resolved atlas of gastric cancer characterises a lymphocyte-aggregated region.

Abstract

The tumour microenvironment is a focal point in cancer immunotherapy: its cellular composition and spatial organisation can affect the clinical outcomes of cancer patients. By integrating single-cell and spatial transcriptomics, we identify four spatial regions and survey how cellular spatial distribution varies across them in gastric cancer. One region, the Lymphocyte Aggregated Region, consists of lymphocyte aggregates and tertiary lymphoid structures. Within it, we observe associations between naive T cell abundance and T cell activation-associated pathways, and correlations exist between distribution patterns of different lymphocytes and two transcriptomically distinct groups - more activated lymphocytes reside in the adjacent cancerous regions of Group A, while more resting lymphocytes settle in those of Group B. Within Group A, PD1⁺CD27⁺ CD8 T cells cluster in closer proximity to CD70⁺LAMP3⁺ dendritic cells. Our study unveils the gastric cancer tumour microenvironment at a spatial resolution and provides insights into the exploration of immunotherapy biomarkers.