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Publication : Peroxynitrite-dependent killing of cancer cells and presentation of released tumor antigens by activated dendritic cells.

First Author  Fraszczak J Year  2010
Journal  J Immunol Volume  184
Issue  4 Pages  1876-84
PubMed ID  20089706 Mgi Jnum  J:159469
Mgi Id  MGI:4443149 Doi  10.4049/jimmunol.0900831
Citation  Fraszczak J, et al. (2010) Peroxynitrite-dependent killing of cancer cells and presentation of released tumor antigens by activated dendritic cells. J Immunol 184(4):1876-84
abstractText  Dendritic cells (DCs), essential for the initiation and regulation of adaptive immune responses, have been used as anticancer vaccines. DCs may also directly trigger tumor cell death. In the current study, we have investigated the tumoricidal and immunostimulatory activities of mouse bone marrow-derived DCs. Our results indicate that these cells acquire killing capabilities toward tumor cells only when activated with LPS or Pam3Cys-SK4. Using different transgenic mouse models including inducible NO synthase or GP91 knockout mice, we have further established that LPS- or Pam3Cys-SK4-activated DC killing activity involves peroxynitrites. Importantly, after killing of cancer cells, DCs are capable of engulfing dead tumor cell fragments and of presenting tumor Ags to specific T lymphocytes. Thus, upon specific stimulation, mouse bone marrow-derived DCs can directly kill tumor cells through a novel peroxynitrite-dependent mechanism and participate at virtually all levels of antitumor immune responses, which reinforces their interest in immunotherapy.
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