Skip to main content
. 2023 Mar 16;14:1052657. doi: 10.3389/fimmu.2023.1052657

Figure 2.

Figure 2

Potential mechanism of tiliroside (TS) enhancing the therapeutic effect of PD-1/PD-L1 inhibitors. HCC cells trigger the metabolic switch from oxidative phosphorylation to aerobic glycolysis in tumor-infiltrating monocytes and macrophages. The activation of HIF1α is induced and consequently the cytokines of TNF-α, IL-10, and IL-1β are produced, which in turn synergistically upregulate the CAXII expression in monocytes and macrophages, and then increase the expression of protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK). CAXII inhibitors (such as TS) can regulate the infiltration of lymphocytes (reducing the ratio of macrophages in total CD45+ cells and increasing the ratio of CD8+ T cells in total tumor lymphocytes) and suppress the expression of vimentin (VIM) and SNAI1 but increase CDH1 by regulating the expression of C-C motif chemokine ligand 8 (CCL8) and PERK, consequently increasing the therapeutic effect of PD-1/PD-L1 inhibitors. HCC, hepatocellular carcinoma; HIF1α, hypoxia-inducible factor (HIF)1α; TNF-α, Tumour necrosis factor α; IL-10, Interleukin 10; IL-1*β, Interleukin-1β; CAXII, carbonic anhydrase XII; SNAI1, Snail Family Transcriptional Repressor 1; CDH1, cadherin 1; PERK, Protein kinase RNA-like endoplasmic reticulum kinase.