Microbiome dysbiosis and immune checkpoint inhibitors: Dual targets in Hepatocellular carcinoma management

Figure 2 Mechanism of action of gut microbiomes and immune checkpoint inhibitors. Gut microbiomes will release metabolites, such as short-chain fatty acids (SCFA) and desamino tyrosine (DAT). SCFA works by entering T cells and inhibiting histone deacetylases (HDAC). Inhibition of HDAC can affect the mechanistic target of rapamycin-ribosomal S6 kinase pathway, which will express cytokines. It leads to the upregulation of programmed cell death 1 ligands and will enhance immunotherapy response. Furthermore, DAT expression may alter gut microbiome composition and balance dysbiosis. DAT also promotes type I interferon signaling, which will promote cytotoxic T-cell and cancer apoptosis, which eventually enhance immune checkpoint inhibitor effectiveness. SCFA: Short-chain fatty acids; DAT: Desamino tyrosine; PD-1: Programmed cell death 1; CTLA-4: Cytotoxic T-lymphocyte-associated protein 4.