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. 2020 Jun 17;8:486. doi: 10.3389/fcell.2020.00486

FIGURE 5.

FIGURE 5

HDAC inhibitors enhance sensitivity to immune checkpoint inhibitors by regulating anti-tumor immune responses. (A) PD-1/PD-L1 interactions between cancer cells and CD8+ T cells suppress T cell activation, leading to tumor tolerance (upper). Ipilimumab, an anti-CTLA-4 antibody, disrupts the interaction between CTLA-4 and CD80/CD86, increasing production of pro-inflammatory cytokines and inducing T cell activation. MDSCs (middle) and TAMs (lower) suppress T cell activation via PD-1/PD-L1 interactions. MDSCs inhibit the function of CD8+ T cells by secreting TGF-β and IL-10. (B) HDAC inhibitors enhance CTL and NK cell activity, induce M1 macrophage polarization, and suppress the immune regulatory function of MDSCs. (C) HDACs regulate the PD-L1 expression to induce CTL activity or apoptosis. BRD4 denotes bromo domain protein 4. (D) HDAC inhibitors enhance sensitivity to PD-L1 blockade by activating CD8+T and NK cells while inactivating MDSCs and M2 macrophages. TAAs denote tumor associated antigens.