Location Matters: Profiling Diffuse Type Gastric Cancer At the Single-Cell Level

Abstract

Spatial single-cell transcriptomics of primary patient diffuse type gastric cancer reveals distinct cancer and stromal cell differences based on location. Expression of CCL2 by stromal cells in deep tumor regions is highlighted as potentially driving the immunosuppressive microenvironment and enhancing (directly or indirectly) the invasive capacity of tumor cells.See related article by Jeong et al., p. 6529.

Figure 1.. Overview of superficial to deep cell transition in diffuse type gastric cancer.

scRNA seq of superficial and deep layer tissues of primary patient diffuse type gastric cancer reveals that epithelial cancer cells, plasma cells and B cells are enriched in the superficial layers, while fibroblasts, endothelial cells, myeloid cells and Tregs tend to localize in the deep layers. In addition, cancer cells in the deep layer acquire a mesenchymal phenotype. The increase of an inflammatory and immunoevasive signature in multiple cell types during the superficial to deep transition is exemplified by the secretion of inflammatory cytokines and chemokines, mainly CCL2, from fibroblasts, endothelial cells and myeloid cells in deeper layers of diffuse type GC.