Programmed Death 1 Ligand Expression in the Monocytes of Patients with Hepatocellular Carcinoma Depends on Tumor Progression

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.