Cell Death Induction by CTL: Perforin/Granzyme B System Dominantly Acts for Cell Death Induction in Human Hepatocellular Carcinoma Cells

Abstract

Cell death induction by cytotoxic T lymphocytes (CTLs) is an important thesis for the understanding of tumor immunotherapy. In the current study we investigated the molecular machinery of CTL-induced cell death in human hepatocellular carcinoma cell lines (HCC lines). CTLs prepared from human peripheral blood induced cell death in all tested HCC lines. As the CTL-induced death system, the effectiveness of Fas ligand/Fas and/or Perforin/Granzyme B systems has been suggested, whereas cell death induction by CTLs was shown independently on Fas expression in the current study. Using various tetrapeptide inhibitors for caspase and its associated factor, we additionally demonstrated that inhibitors for caspase 3 (Ac-DEVD-CHO) and caspase 8/granzyme B (Ac-IETD-CHO) suppressed CTL-induced cell death, but an inhibitor for Fas-activated serine proteinase, which acts for the caspase 3 activator, did not, suggesting that CTL-induced cell death was initiated by the Perforin/Granzyme B system, rather than the Fas ligand/Fas system. On the basis of our current results, we report here that the Perforin/Granzyme B system acts dominantly for the cell death induction of HCC lines.

Hepatocyte Growth Factor Promotes Cell Survival From Fas-Mediated Cell Death in Hepatocellular Carcinoma Cells via Akt Activation and Fas-Death–Inducing Signaling Complex Suppression

“…Tested cell lines were expressing Fas and showed the sensitivity to Fas Ab only in the presence of actinomycin D, consistent with our previous report. 31 Fas-mediated cell death in all tested cell lines was completely suppressed by HGF pretreatment. Especially, SK-Hep1 cells highly expressed Fas (same level as Jurkat) and displayed a sensitivity to agonistic Fas Ab in a dose-dependent manner.…”

iPSC-Derived Regulatory Dendritic Cells Inhibit Allograft Rejection by Generating Alloantigen-Specific Regulatory T Cells

“…As cytotoxic T lymphocyte (CTL)-induced cell death is initiated by the Perforin/Granzyme B pathway (Hayashida et al., 2000), we detected the mRNA expression of Perforin/Granzyme B in allografts. Logically, the levels of both Perforin and Granzyme B were lower in the grafts from iPS-DCregs-treated recipients compared with the grafts from the non-treatment group.…”

Increasing a Robust Antigen-Specific Cytotoxic T Lymphocyte Response by FMDV DNA Vaccination with IL-9 Expressing Construct

“…Tc17 cells, a unique subset of CD8 + T cells, were found in the lung following primary challenge with influenza A and protected against lethal influenza challenge [30, 31]. Cytotoxicity can be induced by two distinct molecular pathways: up-regulation of perforin, or up-regulation of FasL (CD95L) [32, 33]. In our study, we found that high level expressions of IFN- γ and perforin were observed to associate with CD8 + T cells, not the IL-17.…”