A comprehensive metabonomic and transcriptomic analysis reveals how inhibiting glycolysis affects regulatory T cell proliferation
Blocking glycolysis inhibits regulatory T cells (Tregs), which are often hijacked by tumor cells whose survival relies on glycolysis to inhibit antitumor immunity. However, how glycolysis influences Treg proliferation/differentiation remains unclear. Monocarboxylate transporters (MCTs) are key regulatory proteins that affect glycolysis. To describe the potential mechanism underlying the effect of glycolysis on Treg proliferation and differentiation as well as the role of MCT1 on Treg metabolism, we conducted a comprehensive metabonomic and transcriptomic analysis using omics and molecular biology techniques. Fifteen differential metabolites and 2232 differentially expressed genes (DEGs) were identified, which were subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to determine the most widely affected pathways. The results revealed that the adenosine triphosphate-binding cassette (ABC) transporter metabolism pathway was the most differentially activated between these two groups. According to The Cancer Genome Atlas (TCGA) database, the expression of ABC transporter-related genes affects renal clear cell carcinoma prognosis and is closely related to tumor immune cell infiltration. The comprehensive analysis showed that MCT1-induced ABC transporter disorder has important effects on Treg biology. These insights will help to clarify the mechanism of MCT1-induced Treg growth inhibition and emphasize the importance of omics research for deepening the understanding of tumor cell proliferation mechanisms.