Mechanisms for enhanced antitumor immune responses induced by irradiated hepatocellular carcinoma cells engineered to express hepatitis B virus X protein.

ABSTRACT

Tumor associated antigen (TAA) induces both humoral immunity and cellular immunity. The T cell-mediated immune response has an important role in the immune response induced by TAA. The hepatitis B virus X protein (HBx) sequence is mapped with Custer of differentiation (CD)8+ T cell (CTL) epitopes, while a large number of studies have indicated that HBx may enhance the autophagy. In our previous study, a novel hepatocellular carcinoma vaccine was designed that was an irradiated HBx modified hepatocellular carcinoma cell vaccine in autophagic form, which significantly induced antitumor immune responses in vivo. However, the mechanism by which this vaccine contributes to enhancing antitumor immune responses have yet to be fully elucidated. In the present study, we examined how autophagy was induced by this vaccine's influence on the generation of the 'danger signal' by hepatoma tumor cells and the subsequent activation of the immunoresponse. The data showed that the vaccine induced phenotypic maturation of DCs, which leads to efficient cross-presentation and a specific response. Both CD8+ and CD4+ T lymphocytes were involved in the antitumor immune response, as reflected by IFN-γ secretion. In addition, damage-associated molecular pattern molecules (DAMPs) were significantly elevated in the vaccine, and the elevation of DAMPs was autophagy-dependent. Furthermore, the antitumor activity was achieved by adoptive transfer of lymphocytes but not serum. The present findings indicated that this vaccine enhanced antitumor immune responses, which was in accordance with our previous study.