In recent years, immune checkpoint inhibitors (anti-PD-1, anti-PD-L1, and anti-CTLA-4 antibodies) have exhibited potential therapeutic effects for advanced HCC.
Concomitant with patient-derived M-MDSC suppression by i-BET762, combined treatment with anti-PD-L1 synergistically enhanced TILs, resulting in tumour eradication and prolonged survival in the fibrotic-HCC mouse model.
Finally, using SP263, the mean number of PD-L1-positive cells was 11.3 ± 12.6 in HCC from deceased patients, versus 4.7 ± 5.2 in alive patients (p = 0.039).
We further demonstrated that OPN facilitates chemotactic migration, and alternative activation of macrophages, and promotes the PD-L1 expression in HCC via activation of the CSF1-CSF1R pathway in macrophages.
High circulating PD-L1 (HR 0.12, 95%CI 0.16-0.86, p = 0.011) and high circulating Galectin-9 (HR 0.11, 95%CI 0.15-0.85, p = 0.010) levels were both associated with improved HCC-specific survival.
The correlation between paired serum sPD-L1 levels and tumor PD-L1 expression (in resected tissue homogenates) was assessed in a separate group of 20 patients with HBV-related HCC.
Furthermore, we performed an extensive immunomonitoring of patients with HCC treated with sorafenib or programmed death (PD)-1/PD-L1 pathway blockade using multiparametric flow cytometry.
High programmed death ligand 1 expression and high frequency of cell cycle regulatory gene alterations were found in the LCC-Null group offering alternative options of targeted therapy.
To our best knowledge we firstly found that PD-1/PD-L1 mediated exhaustion of infiltrated NK cells promoted hepatocellular carcinoma progression under depression and provided a novel strategy for GC-mediated anti-depressant therapy in liver cancer patients.
Blocking the PD-1/PD-L1 axis in dendritic cell-stimulated Cytokine-Induced Killer Cells with pembrolizumab enhances their therapeutic effects against hepatocellular carcinoma.
The epigenetic modificator EZH2 can suppress the expression of immune checkpoint inhibitor PD-L1 by directly upregulating the promoter H3K27me3 levels of CD274 and IRF1 in hepatoma cells, and might serve as a potential therapeutic target for combination of immunotherapy for immune-activated HCC.
PD-L1 expression was positively correlated with MMP-12 expression, indicating that MMP-12 may promote the development of HCC through the up-regulation of PD-L1.