Increased Expression of Myeloid-Derived Suppressor Cells in Patients with HBV-Related Hepatocellular Carcinoma

Abstract

Background and Aim. Myeloid-derived suppressor cells (MDSCs) have attracted attention due to their important role in tumor immune escape. Several studies have investigated the involvement of MDSCs into hepatocellular carcinoma (HCC); however, due to the difference of MDSC phenotype, patient types, and sample source among the studies, the results were inconsistent and controversial. The present study aimed to confirm the expression and clinical significance of MDSCs in HBV-related HCC patients. Methods. The percentages of MDSCs, IFN-γ-producing CD4 and CD8 T cells in the peripheral blood of HCC patients, chronic hepatitis B (CHB) patients, and healthy controls (HC) were determined by flow cytometry. The serum concentrations of IL-10 and TNF-α were determined by ELISA. The association of the percentages of MDSCs with tumor burden, liver function parameters, systemic inflammation-related indexes, and IFN-γ-producing T cells was assessed. Results. The percentages of MDSCs and PMN-MDSCs were significantly higher in HCC patients than those in CHB patients and HC. The level of MDSCs was correlated with indirect bilirubin and prealbumin, as well as systemic inflammation response index, monocyte/lymphocyte ratio, and monocyte counts. The frequency of IFN-γ-producing CD8 T cells of HCC patients was lower than that of HC. However, there was no relationship between MDSCs and IFN-γ-producing CD8 T cells. The level of IL-10 in HCC patients was significantly higher than that in CHB patients. Conclusion. MDSCs seem to play an important role in the process leading from chronic HBV infection to HCC. Early inhibiting these cells could affect tumor progression.

The Functional Roles of Immune Cells in Primary Liver Cancer

“…49 High percentages of MDSCs in HCC patients are correlated with monocyte counts, suggesting that MDSCs may be involved in immune cell infiltration, although detailed mechanisms are still undefined. 50 MDSCs are heterogeneous and can be classified into two subsets: monocytic MDSCs, with monocyte-like morphologic characteristics, and polymorphonuclear MDSCs (PMN-MDSCs), showing morphologic characteristics of neutrophils. 51 MDSCs can be a therapeutic target by depletion of MDSCs, inhibition of MDSC trafficking, or blocking the immunosuppressive function of MDSCs.…”

Immunopathology of Chronic Hepatitis B Infection: Role of Innate and Adaptive Immune Response in Disease Progression

“…Although MDSCs are associated with protective function in acute liver inflammation, these cells facilitate inflammation and tissue damage during chronic liver disease. The expansion of MDSCs has been reported during chronic HBV infection, which favors T cell exhaustion and establishment of persistent HBV infection [ 36 , 37 ]. The frequencies of circulating MDSCs were higher in HBeAg-positive patients than HBeAg-negative.…”

Deciphering the roles of myeloid derived suppressor cells in viral oncogenesis

“…However, the mechanisms behind this dysfunctional response are not fully understood. MDSCs are significantly expanded in CHB patients ( 60 , 149 – 154 ), indicating a potential role in preventing viral clearance.…”