Exhausted CD8+ T cells overexpress CCL5 during combination therapy to mediate resistance of hepatoma cells to lenvatinib: one situation may contribute to the survival of residual tumor cells
In conclusion, we discovered that during combination therapy, tumor tissue demonstrated a more active metabolic reprogramming than normal liver tissue, as indicated by a significant upregulation of CYP1A1 expression. In addition, we validated that CD8T cells secreted more CCL5 after treatment, which upregulated CYP1A1 expression by binding to CCR5, leading to resistance of hepatoma cells to lenvatinib. Finally, we demonstrated that interference with the CCL5/CCR5/CYP1A1 pathway can enhance the efficacy of lenvatinib and combination therapy. Overall design: The Huh7 cells were divided into experimental and control groups. Three replicates were set for each group of samples.The experimental group was stimulated with 100ng/ml of CCL5, while the control group was stimulated with an equal volume of ddH2O. After 24 hours of stimulation, the Huh7 cells were washed with PBS and lysed using TRIzol for RNA extraction to perform RNAseq.