Single cell RNA-seq reveals immunosuppressive gastric stem-like cancer cells as a poor prognostic factor
Hong Kai Lee,
Kok Siong Ang,
Jia Chi Tan,
Sergio Erdal Irac,
Ze Ming Lim,
Charles Antoine Dutertre,
Mai Chan Lau,
Chun Jye Lim,
Samuel Wen Jin Chuah,
Joe Poh Sheng Yeong,
Matthew Chau Hsien Ng,
Shanshan Wu Howland,
Wei Peng Yong,
Posted 23 Oct 2020
bioRxiv DOI: 10.1101/2020.10.23.351726
Posted 23 Oct 2020
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. ### Competing Interest Statement The authors have declared no competing interest.
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