Hypoxia-Induced Immunosuppression in Kidney Carcinoma Cells

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most prevalent subtype of renal cell carcinoma and accounts for 70-80% of all kidney tumors. It originates in the proximal convoluted tubules in the nephron and is characterized by cells with clear cytoplasm due to large intracellular lipid droplets and free cholesterol. The current study examined the impact of hypoxia on kidney carcinoma cells 786-0. MATERIAL AND METHODS: A publicly available dataset GSE225253 was analyzed, which contains RNA-seq transcriptomic data of kidney carcinoma cells 786-0 subject to normoxic and hypoxic conditions. Differential gene expression (DGE) analysis and gene ontology (GO) enrichment analysis were performed by R packages. RESULTS: Following hypoxia, 2366 genes were upregulated and 1799 were downregulated in 786-0 cells (FDR < 0.05). GO enrichment analysis revealed key upregulated pathways including upregulation of cell adhesion, gland development, and monosaccharide metabolic process, and downregulated pathways including ribonucleoprotein complex biogenesis, RNA splicing, and ribosome biogenesis. Hypoxia induced higher expression levels of growth factors (IGF2, CSF1, CSF2, TGFB1, TGFB2, VEGFA), inflammatory chemokines (CCL2, CXCL16) and cytokines (IL12A, IL32), and immune checkpoint ligands and receptors (CD274, PDCD1LG2, CD276, TNFRSF9, ADORA2A, TNFRSF14) in 786-0 cells. CONCLUSION: Hypoxia induced significant gene expression changes in kidney carcinoma cells, enhancing growth factor signaling, inflammation, immune checkpoint expression, and angiogenesis. These changes likely contribute to a tumor-supportive microenvironment, promoting cancer cell survival, proliferation, and immune evasion. Further in vitro and ex vivo studies are warranted to validate these findings and explore potential therapeutic strategies targeting hypoxia-induced pathways in ccRCC. in body composition features are associated with survival.