Background/AimsHepatitis B virus (HBV) is the major cause of chronic liver disease in Korea, but viral prevalence has decreased because of hepatitis B vaccination programs. In this study, we investigated longitudinal changes in HBV in fection in the general Korean population.MethodsHBV surface antigen (hepatitis B surface antigen, HBsAg) seropositivity was assessed from the Korea National Health and Nutrition Examination Survey (I to V). In total, 50,140 subjects were tested for serum HBsAg positivity over a period of 12 years (1998 to 2010).ResultsThe prevalence of HBsAg seropositivity decreased over the study period. The rates of HBsAg carriers were 4.61% in 1998, 4.60% in 2001, 3.69% in 2005, 3.01% in 2008, and 2.98% in 2010 (p < 0.0001). The reduction in HBV infection rates was more prominent in younger age groups. Among teenagers (10 to 19 years), the percentage of HBsAg carriers decreased from 2.2% in 1998 to 0.12% in 2010 (p < 0.0001). Among those aged 10 to 39 years, the percentage of HBV infection decreased from 4.72% in 1998 to 2.29% in 2010 (p < 0.0001). However, no decreasing trend in HBsAg positivity was observed among those aged 50 or older (p > 0.05). Neither gender nor socioeconomic status were associated with the decreased prevalence of HBsAg carriers.ConclusionsHBV infection has decreased in the Korean population since the advent of vaccination programs. However, the decrease is limited to the younger population, and viral persistence remains in the middle-aged and older population.

These data suggest that the novel TCR-targeting LMP1 might allow the potential design of T-cell-based immunotherapeutic strategies against EBV-positive malignancies.

MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression by suppressing translation or facilitating mRNA decay. Differential expression of miRNAs is involved in the pathogenesis of several diseases including cancer. Here, we investigated the role of-miR-24-3p as a downregulated miRNA in metastatic cancer. miR-24-3p was decreased in metastatic cancer and lower expression of miR-24-3p was related to poor survival of cancer patients. Consistently, ectopic expression of miR-24-3p suppressed the cell migration, invasion, and proliferation of MCF7, Hep3B, B16F10, SK-Hep1, and PC-3 cells by directly targeting p130Cas. Stable expression of p130Cas restored miR-24-3p-mediated inhibition of cell migration and invasion. These results suggest that miR-24-3p functions as a tumor suppressor and the miR-24-3p/p130Cas axis is a novel factor of cancer progression by regulating cell migration and invasion.

Activated B-cells are a promising alternative source of antigen-presenting cells. They can generally be obtained in sufficient numbers for clinical use, but in most instances produce weak immune responses and therapeutic effects that are suboptimal for use in therapeutic cancer vaccines. To improve the immunogenic potency and therapeutic efficacy of B-cell-based vaccines, ex vivo-activated B-cells were transduced with recombinant lentiviruses in order to express additional costimulatory ligands—CD40L, CD70, OX40L, or 4-1BBL—either individually or in pairs (CD70/CD40L, OX40L/CD40L, or 4-1BBL/CD40L). We observed that the expression of CD40L molecules on B-cells was crucial for T-cell priming and activation. Administration of B-cells co-expressing CD40L with the other costimulatory ligands provided substantial antigen-specific CD8 T-cell responses capable of provoking in vivo proliferation and potent cytolytic activities. Notably, expression of CD40L augmented B-cell viability by inhibiting apoptosis through upregulated expression of the anti-apoptotic molecules BCL2, Bcl-xL and Bax. B-cells co-expressing CD40L with CD70, OX40L, or 4-1BBL induced potent therapeutic antitumor effects in a B16 melanoma model. Moreover, the combination of genetically-modified B-cell vaccines with programmed cell death-1 blockade potentiated the therapeutic efficacy. These results suggest that B-cells endowed with additional costimulatory ligands enable the design of effective vaccination strategies against cancer.

PurposeSuccessful tumor eradication primarily depends on generation and maintenance of a large population of tumor-reactive CD8 T cells. Dendritic cells (DCs) are well-known potent antigen-presenting cells and have applied to clinics as potent antitumor therapeutic agents. However, high cost and difficulty in obtaining sufficient amounts for clinical use are the crucial drawbacks of DC-based vaccines. Here, we aimed to develop T cell–based vaccine capable of eliciting potent antitumor therapeutic effects by providing effective costimulatory signals.Materials and MethodsAntigenic peptide-loaded T cells transfected with retrovirus encoding costimulatory ligands CD70, CD80, OX40L, or 4-1BBL were assessed for antigen-specific CD8 T-cell responses and evaluated antitumor effects along with immunization of a mixture of synthetic peptides, poly-IC and anti-CD40 antibodies (TriVax).ResultsT cells expressing CD70 (CD70-T) exhibited similar level of stimulatory functionality and therapeutic efficacy as DCs. Moreover, CD70-T prime followed by TriVax booster heterologous vaccination elicited therapeutic antitumor effect against B16 melanoma where mediated by CD8 T cells but not CD4 T cells or natural killer cells. The combination with programmed death-ligand 1 blockade led to potent therapeutic efficacy which exhibited increased tumor-infiltrating CD8 T cells. CD70-T pulsed with multi-antigenic peptide generated multiple antigen-specific polyvalent CD8 T cells that were capable of inhibiting tumor growth effectively. Moreover, CD70-T vaccination resulted in higher expansion and migration of adoptively transferred T cells into tumor sites and elicits enhanced therapeutic effects with peptide-based booster immu-nization.ConclusionThese results imply that T cells endowed with CD70 enable the design of effective vaccination strategies against solid cancer, which may overcome current limitations of DC-based vaccines.