Abstract
Snail is a major transcriptional factor that induces epithelial-mesenchymal transition (EMT). In this study, we explore the effect of Snail on tumor immunity. Snail knockdown in mouse ovarian cancer cells suppresses tumor growth in immunocompetent mice, associated with an increase of CD8+ tumor-infiltrating lymphocytes and a decrease of myeloid-derived suppressor cells (MDSCs). Snail knockdown reduces the expression of CXCR2 ligands (CXCL1 and CXCL2), chemokines that attract MDSCs to the tumor via CXCR2. Snail upregulates CXCR ligands through NF-kB pathway, and most likely, through direct binding to the promoters. A CXCR2 antagonist suppresses MDSC infiltration and delays tumor growth in Snail-expressing mouse tumors. Ovarian cancer patients show elevated serum CXCL1/2, which correlates with Snail expression, MDSC infiltration, and short overall survival. Thus, Snail induces cancer progression via upregulation of CXCR2 ligands and recruitment of MDSCs. Blocking CXCR2 represents an immunological therapeutic approach to inhibit progression of Snail-high tumors undergoing EMT.
Highlights
Snail is a major transcriptional factor that induces epithelial-mesenchymal transition (EMT)
We first analyzed the dataset of high-grade serous ovarian cancer (HGSOC) from The Cancer Genome Atlas (TCGA) (n = 266)
epithelial-to-mesenchymal transition (EMT) has been widely accepted as a key process for tumor invasion and metastasis, since the loose cell–cell contacts and high motility derived from EMT facilitate tumor cell detachment from basement membrane and tumor invasion into the surrounding stroma or vessels[16,20]
Summary
Snail is a major transcriptional factor that induces epithelial-mesenchymal transition (EMT). Snail knockdown in mouse ovarian cancer cells suppresses tumor growth in immunocompetent mice, associated with an increase of CD8+ tumor-infiltrating lymphocytes and a decrease of myeloid-derived suppressor cells (MDSCs). Snail induces cancer progression via upregulation of CXCR2 ligands and recruitment of MDSCs. Blocking CXCR2 represents an immunological therapeutic approach to inhibit progression of Snail-high tumors undergoing EMT. We previously reported that MDSC infiltration was inversely correlated with CD8+TIL numbers and shorter overall survival in advanced ovarian cancer[14]. These reports indicated that MDSCs, as key players in cancer immune evasion, might be used both as prognostic factors and as therapeutic targets in cancer treatment.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
