We showed that a fraction of monocytes/Mphi in peritumoral stroma, but not in cancer nests, expresses surface PD-L1 (also termed B7-H1) molecules in tumors from patients with hepatocellular carcinoma (HCC).
Our results suggest that the expression of B7-H1 in hepatocarcimona cells can be initiated by HBx antigen, thus inducing T cell apoptosis and finally potentially facilitates the genesis of HCC.
In this study, we investigated the mechanisms by which the chemotherapeutic agent paclitaxel (PTX) induced the expression of B7-H1 immunosuppressive molecules in the human colorectal adenocarcinoma cell line SW480 and the hepatocellular carcinoma cell line HepG2.
Therefore, this study extends our knowledge of the role of the PD-1/PD-L1 pathway in tumor evasion and provides evidence for a new therapeutic target in HCC patients.
These results suggest that overexpression of B7-H1 in HCC may be induced by inflammatory microenvironment involving macrophages and imply that anti-inflammation therapy might be preventive for immune escape and assistant for immunotherapy of 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.
The expression of PD-L1 is associated with the survival time of patients with hepatocellular carcinoma, and the median survival time of patients with high expression of PD-L1 is ten months.
We found approximately 25% of HCCs to have markers of an inflammatory response, with high expression levels of the CD274 molecule (programmed death-ligand 1) and programmed cell death 1, markers of cytolytic activity, and fewer chromosomal aberrations.
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).
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.
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.
Positive Expression of Programmed Death Ligand 1 in Peritumoral Liver Tissue is Associated with Poor Survival after Curative Resection of Hepatocellular Carcinoma.
These cells also express programmed death ligand 1 (PD-L1) and interleukin-10, and directly suppress liver cytotoxic CD8<sup>+</sup> T lymphocytes, which prevent emergence of hepatocellular carcinoma and express a limited repertoire of T-cell receptors against tumour-associated antigens.
Using this approach, we preferentially and efficiently inactivated RAF/ERK, upregulated BIM and down-regulated PD-L1 expression in HCC, and facilitated intra-tumoral infiltration of cytotoxic CD8+ T cells.
Furthermore, early trials have demonstrated the efficacy and safety of targeting PD-1/PD-L1 as an emerging field in the management of patients with advanced hepatocellular carcinoma.
Expression of CXCL12, PD-L1 and of surrogate markers for tumour hypoxia was evaluated at messenger RNA (mRNA) level in a cohort of HCC patients from The Cancer Genome Atlas and immunohistochemically in an independent cohort from the University Hospital of Bonn.