Our results indicated that three functional polymorphisms (rs2297136, rs4143815 and rs17718883) of the PD-L1 gene were associated with HCC risk and prognosis, suggesting that genetic variants of PD-L1 polymorphisms might be a possible prognostic marker for the prediction of HCC risk and development.
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.
Hence, our observation confirmed that miR-570 works as proliferation and metastatic suppressor in hepatocellular carcinoma cells through directly targeting B7-H1 in hepatocellular carcinoma cell and rationally presents that miR-570 has the potential to be a useful clinical noninvasive diagnostics or predictive marker in human hepatocellular carcinoma.
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.
Results of combination treatment with the anti-PD-L1 antibody durvalumab and the anti-CTLA-4 antibody tremelimumab in HCC were presented at the 2017 annual meeting of the ASCO (American Society of Clinical Oncology).
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.
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.
At the same time, a combinational therapy with HIF-1α inhibitors in conjunction with PD-L1 blockade may be beneficial for HCC patients with co-overexpression in the future.
Although there was no significant difference of PD-L1 expression on CD14<sup>+</sup> population among three disease groups, further analysis demonstrated that the frequency of CD14<sup>+</sup>PD-L1<sup>+</sup> population was negatively correlated with HBV DNA load, the levels of alanine aminotransaminase (ALT), and the levels of aspartate aminotransferase (AST), respectively, at CHB stage, while it did not present significant correlation with such parameters at LC stage and was only positively correlated with HBV DNA load at HCC stage.
The combination of anti-PD-L1 and radiation significantly improved the antitumor effect shown in tumor growth delay as well as in survival, supporting a novel combination strategy of immunoradiotherapy in 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.
Furthermore, PD-L1 overexpresion was significantly associated with poor DFS/PFS in patients with hepatocellular carcinoma (HCC) (HR = 1.72, 95% CI = 1.21-2.46, P = .003), melanoma (HR = 3.39, 95% CI = 2.02-5.69, P <.000), and renal carcinoma, (HR = 5.04, 95% CI = 2.87-8.86, P <.000).
The combination of anti-PD-1/PD-L1 and anti-CTLA-4 antibodies is being evaluated in other phase I/II trials, and the results suggest that an anti-PD-1 antibody combined with locoregional therapy or other molecular targeted agents is an effective treatment strategy for HCC.
Monoclonal antibodies (mAbs) that target the programmed cell death‑1 (PD‑1/PDCD1)/programmed death-ligand 1 (PD-L1) immune checkpoint have demonstrated substantial clinical benefit for a variety of solid tumors; however, these mAbs have not been well studied in HCC.