Proliferative and quiescent human gastric cancer stem-like cells are associated with differential chemoresistance and patient mortality

Abstract

The tumor microenvironment is characterized by high cellular heterogeneity and a complex network of cell-cell communications. Analysis at the single cell level is required to dissect this complexity. Here we apply single-cell full-length transcriptome sequencing to analyze 3443 cells from paired normal-adjacent and tumor tissues of 15 gastric cancer patients with different histological profiles. Among the epithelial cells profiled, we discovered subsets of proliferative stem-like cells with upregulated pro-tumor pathways and that were associated with poorer prognosis. Stem-like cell enriched tissues also show distinct T cell populations with proportionally more TIM3+ CD8+ cells, while non-enriched tissues had proportionally more KLRC1+ CD8+ cells, offering opportunities for checkpoint inhibitor therapy. In silico predictions of ligand-receptor interactions revealed immune-suppressive interactions between these stem-like cells and immune cells via interacting pairs such as Nectin-2(CD112)-TIGIT, Galectin-9-TIM3 and CXCL16-CXCR6. Using immunohistochemistry, we found CD8+ T cells expressing TIGIT in close proximity to stem-like cells expressing NECTIN2.

Papillary Thyroid Carcinoma Landscape and Its Immunological Link With Hashimoto Thyroiditis at Single-Cell Resolution

“…We adopted CellphoneDB to detect common ligand-receptor interactions in thyroid cancer that have been alternately verified in other cancers recently (Chen et al, 2020;Lee et al, 2020). Dot plots showed selected ligand-receptor interactions starting from follicular epithelial cells to immune cells in adjacent tissue and tumor samples from PTC patients with concurrent HT, respectively, (Figures 6E,F).…”

Data_Sheet_1.PDF

“…We adopted CellphoneDB to detect common ligand-receptor interactions in thyroid cancer that have been alternately verified in other cancers recently (Chen et al, 2020;Lee et al, 2020). Dot plots showed selected ligand-receptor interactions starting from follicular epithelial cells to immune cells in adjacent tissue and tumor samples from PTC patients with concurrent HT, respectively, (Figures 6E,F).…”