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.