About: Human Tumor Cells Killed by Anthracyclines Induce a Tumor-Specific Immune Response     Goto   Sponge   NotDistinct   Permalink

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Description
  • 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-gamma-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. Cancer Res; 71(14); 4821-33. (C) 2011 AACR.
  • 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-gamma-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. Cancer Res; 71(14); 4821-33. (C) 2011 AACR. (en)
Title
  • Human Tumor Cells Killed by Anthracyclines Induce a Tumor-Specific Immune Response
  • Human Tumor Cells Killed by Anthracyclines Induce a Tumor-Specific Immune Response (en)
skos:prefLabel
  • Human Tumor Cells Killed by Anthracyclines Induce a Tumor-Specific Immune Response
  • Human Tumor Cells Killed by Anthracyclines Induce a Tumor-Specific Immune Response (en)
skos:notation
  • RIV/00216208:11130/11:7037!RIV12-MSM-11130___
http://linked.open...avai/predkladatel
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • I
http://linked.open...iv/cisloPeriodika
  • 14
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  • 202980
http://linked.open...ai/riv/idVysledku
  • RIV/00216208:11130/11:7037
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • group box-1 protein; toll-like receptors; dendritic cells; calreticulin exposure; cross-presentation; necrotic cells; t-cells; cancer; death; immunogenicity (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • US - Spojené státy americké
http://linked.open...ontrolniKodProRIV
  • [76E35B2745E9]
http://linked.open...i/riv/nazevZdroje
  • Cancer Research
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
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http://linked.open...UplatneniVysledku
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  • 71
http://linked.open...iv/tvurceVysledku
  • Rob, Lukáš
  • Brtnický, Tomáš
  • Fučíková, Jitka
  • Špíšek, Radek
  • Bartůňková, Jiřina
  • Fialová, Anna
  • Králíková, Petra
http://linked.open...ain/vavai/riv/wos
  • 000292763700010
issn
  • 0008-5472
number of pages
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  • 11130
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