As preliminary step toward this goal, we have investigated the expression of antigen presenting molecules (HLA class I and class II) and immune checkpoints (PD-1 and PD-L1) in 43 HCC samples from distinct patients and in HCC cell lines.
Nuclear grade, RGS5 expression, and EpCAM expression were significantly higher in the PD-L1-positive HCC group compared with the PD-L1-negative HCC group (P<0.05).
Furthermore, CT significantly inhibited the growth of syngeneic Hepa1-6 hepatoma tumors, and, in combination with anti-PD-L1 cured Hepa1-6-bearing mice with the induction of long-term anti-Hepa1-6 specific immunity.
Overexpression of PD-L1 in tumor cells and PD-1 on tumor-infiltrating T cells has been associated with poorer prognosis, more advanced disease and higher recurrence rates in HCC.
Blocking the programmed death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway in hepatocellular carcinoma (HCC) is a very promising approach in immunotherapy.
These results suggested the potential of icaritin as a novel oral immunotherapy for advanced HCC in addition to antibody-based PD-1/PD-L1 blockade therapies.
Intriguingly, HDAC6-depleted T cells triggers PD-1-PD-L1 expression to achieve a strong synergistic effect to sensitize advanced HCC to immune checkpoint blocker, while blockade of IL-17A partially suppresses it.
This review provides an overview of the most recent data pertaining to predictive factors for response to PD-1/PD-L1 checkpoint inhibition in the field of HCC.
<b>Methods:</b> In an observational study of HCC liver samples, we determined the incidence of PD-L1 and immune cell (IC) infiltrates, and signs of TGF-β activity.
Regarding tumor-infiltrating macrophages, we observed a significantly higher expression of markers associated with M2 phenotype and a higher expression of PD-L1 in patients with HCC in comparison to CCA.
Global hypermethylation, and expression of PD-1 and PD-L1 in TILs, and PD-L1 in tumors, were also associated with HCC-IS (p <0.001), whereas human leukocyte antigen type did not differ according to HCC type or EBV positivity.
However, the interaction of programmed cell death 1 (PD-1) and PD-L1-mediated T-cell inhibition is involved in immune evasion in a wide range of solid tumors, including HCC.
Besides oncolytic viruses, vaccines, or immune cell infusions, first results from early-phase clinical trials particularly encourage the use of immune checkpoint inhibitors against PD-1/PD-L1 and CTLA-4 for HCC.
To better characterise PD-L1 expression in hepatocellular carcinoma (HCC), we analysed its expression patterns in 453 HCC patients by double staining for CD68 and PD-L1 using the Tyramide Signal Amplification Systems combined with immunohistochemistry.
Besides, celecoxib treatment increased the infiltration of cytotoxic T lymphocytes (CTLs) and reduced the number of regulatory T cells (Tregs), tumor-associated macrophages (TAMs), and the expression of immune checkpoint PD-L1 in HCC tissues during epirubicin therapy.
Additionally, the disruption of PD-1 could protect the GPC3-CAR T cells from exhaustion when combating with native PD-L1-expressing HCC, as the levels of Akt phosphorylation and anti-apoptotic protein Bcl-xL expression in PD-1 deficient GPC3-CAR T cells were significantly higher than those in wild-type GPC3-CAR T cells after coculturing with PLC/PRF/5.