Abstract
Monocytes (CD14+ cells) from advanced-stage hepatocellular carcinoma (HCC) patients express programmed death 1 ligand (PD-L)/PD-1 and suppress the host antitumor immune response. However, it is unclear whether cancer progression is associated with CD14+ cells. We compared CD14+ cell properties before and after cancer progression in the same HCC patients and examined their role in antitumor immunity. CD14+ cells were isolated from 15 naïve early-stage HCC patients before treatment initiation and after cancer progression to advanced stages. Although CD14+ cells from patients at early HCC stages exhibited antitumor activity in humanized murine chimera, CD14+ cells from the same patients after progression to advanced stages lacked this activity. Moreover, CD14+ cells from early HCC stages scantly expressed PD-L1 and PD-L2 and produced few cytokines, while CD14+ cells from advanced stages showed increased PD-L expression and produced IL-10 and CCL1. CD14+ cells were also isolated from five naïve advanced-stage HCC patients before treatment as well as after treatment-induced tumor regression. The CD14+ cells from patients with advanced-stage HCC expressed PD-L expressions, produced IL-10 and CCL1, and exhibited minimal tumoricidal activity. After treatment-induced tumor regression, CD14+ cells from the same patients did not express PD-Ls, failed to produce cytokines, and recovered tumoricidal activity. These results indicate that PD-L expression as well as CD14+ cell phenotype depend on the tumor stage in HCC patients. PD-L expressions of monocytes may be used as a new marker in the classification of cancer progression in HCC.
Highlights
Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death worldwide
In our recent report, we showed that the monocytes of patients with advanced-stage HCC expressed PD-L1 and PD-L2 and suppressed the antitumor immune response of other effector cells
(considered to be the M2b phenotype). These results suggest that circulating monocytes from patients with advanced stages of HCC had already become skewed toward the M2b phenotype in the peripheral blood by the influence of tumor-associating factors
Summary
Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death worldwide. The World Health Organization estimates that more than 1 million individuals will die from HCC in 2030 [1]. The majority of cases occur in patients with liver disease, mostly as a result of hepatitis B or C virus (HBV or HCV) infection, alcohol abuse, or nonalcoholic steatohepatitis. The five-year survival rate of HCC patients is only 18%, making it the second most lethal tumor [2]. Therapeutic options are primarily selected on the basis of tumor stage and the extent of liver dysfunction. HCC was treated by surgical resection or radiofrequency ablation. Frequent synchronous or metachronous recurrence in the form of new tumors or intrahepatic metastases led to high mortality rates in HCC patients [3]
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