Immunogenic cell death is characterized by the early surface exposure of chaperones including calreticulin and HSPs, which affect dendritic cell (DC) maturation and the uptake and presentation of tumor antigens. It has also been shown that it is characterized by the late release of high mobility group box 1 (HMGB1), which acts through Toll-like receptor 4 (TLR4) and augments the presentation of antigens from dying tumor cells to DCs. Most of the data on immunogenic tumor cell death were obtained using mouse models. In this study, we investigated the capacity of clinically used chemotherapeutics to induce immunogenic cell death in human tumor cell lines and primary tumor cells. We found that only anthracyclines induced a rapid translocation of calreticulin, HSP70, and HSP90 to the cell surface and the release of HMGB1 12 hours after the treatment. The interaction of immature DCs with immunogenic tumor cells led to an increased tumor cell uptake and induces moderate phenotypic maturation of DCs. Killed tumor cell-loaded DCs efficiently stimulated tumor-specific IFN-γ-producing T cells. DCs pulsed with killed immunogenic tumor cells also induced significantly lower numbers of regulatory T cells than those pulsed with nonimmunogenic tumor cells. These data indicate that human prostate cancer, ovarian cancer, and acute lymphoblastic leukemia cells share the key features of immunogenic cell death with mice tumor cells. These data also identify anthracyclines as anticancer drugs capable of inducing immunogenic cell death in sensitive human tumor cells.

• MeSH
• akutní lymfatická leukemie farmakoterapie   imunologie   patologie   MeSH
• antracykliny imunologie   farmakologie   MeSH
• buněčná smrt účinky léků   imunologie   MeSH
• dendritické buňky imunologie   patologie   MeSH
• fagocytóza účinky léků   imunologie   MeSH
• kalretikulin biosyntéza   imunologie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádory prostaty farmakoterapie   imunologie   patologie   MeSH
• nádory vaječníků farmakoterapie   imunologie   patologie   MeSH
• nádory farmakoterapie   imunologie   patologie   MeSH
• protein HMGB1 imunologie   sekrece   MeSH
• proteiny tepelného šoku HSP70 biosyntéza   imunologie   MeSH
• proteiny tepelného šoku HSP90 biosyntéza   imunologie   MeSH
• T-lymfocyty účinky léků   imunologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH