Fig. 9: TCA incapacitates CD8+ T cells via the MAPK/ERK pathway.

A Volcano plot comparing the mRNA profiles analysed with RNA-seq of CD8+ T cells isolated from the Hepa1-6 tumours of the TCA-treated and control mice. B Heatmaps illustrating the relative expression of signature genes in CD8+ T cells derived from the TCA-treated and control mice. C KEGG pathway enrichment analysis and D Analysis of GO- BP (biological process) terms of downregulated genes in the TCA-treated CD8+ T cells. The top 20 identified pathways are presented. E CD8+ T cells isolated from naïve WT mice and treated with different doses of TCA were analysed for the phosphorylation of ERK, P38, JNK, and P65 by immunoblotting. Column plots depict the relative band intensity ratios of phosphorylated/total proteins, and the relative expression was normalized to that of RPS-18. F–H Effects of treatment with TCA with or without C16-PAF on the phosphorylation of ERK (F), proliferation, and expression of cytotoxic cytokines and chemokine receptors at the transcript and protein levels in CD8+ T cells, as determined by flow cytometry (G) and qPCR (H). The data are presented as the means ± SEMs. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, and ns not significant. TCA taurocholic acid, KEGG Kyoto Encyclopedia of Genes and Genomes, GO-BP Gene Ontology biological process terms, WT wild type, q-PCR quantitative real-time PCR.