Decreased granzyme-B expression in CD11c(+)CD8(+) T cells associated with disease progression in patients with HBV-related hepatocellular carcinoma

INTRODUCTION: CD11c(+)CD8(+) T cells are an unconventional CD8(+) T cell subset that exerts antiviral activity in infectious diseases. However, its characteristics in hepatocellular carcinoma (HCC) have not been elucidated. METHODS: Twenty-six patients with hepatitis B virus (HBV)-related HCC and 25 healthy controls (HC) were enrolled. The frequency and phenotype of CD11c(+)CD8(+) T cells in peripheral blood and tumors in situ were detected by flow cytometry and immunohistochemistry. RESULTS: Both the HCC group and HC group had similar frequency and phenotype characteristics of CD11c(+)CD8(+) T cells in the periphery. CD11c(+)CD8(+) T cells were mainly composed of effector T cells, most of which were CD45RA(+)CCR7-. Compared with CD11c-CD8(+) T cells, CD11c(+)CD8(+) T cells had a higher proportion of CD38 and HLA-DR double positive, and expressed high levels of granzyme-B (GB) and degranulation marker CD107a, and produced high levels of interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-α) and interferon-gamma (IFN-γ). However, the ability of degranulation and TNF-α production of CD11c(+)CD8(+) T cells in patients with HCC were significantly lower than that in healthy controls. The GB expression level of peripheral CD11c(+)CD8(+) T cells in patients with advanced stage of HCC was significantly lower than that in patients with early stage of HCC, and the GB expression level of liver-infiltrating CD11c(+)CD8(+) T cells in tumor tissues was lower than that in non-tumor tissues. More importantly, the GB expression level of peripheral CD11c(+)CD8(+) T cells was negatively correlated with tumor volume. CONCLUSIONS: These findings indicate that CD11c(+)CD8(+) T cells may have potential anti-tumor activity and that GB(+)CD11c(+)CD8(+) T cells are associated with disease progression in patients with HBV-related HCC.