Peroxynitrite-dependent killing of cancer cells and presentation of released tumor antigens by activated dendritic cells.
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.
Fraszczak
Jennifer
J
Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 866, Institut de Recherche Fédératif 100, Université de Bourgogne, Dijon, France.
Trad
Malika
M
Janikashvili
Nona
N
Cathelin
Dominique
D
Lakomy
Daniela
D
Granci
Virginie
V
Morizot
Alexandre
A
Audia
Sylvain
S
Micheau
Olivier
O
Lagrost
Laurent
L
Katsanis
Emmanuel
E
Solary
Eric
E
Larmonier
Nicolas
N
Bonnotte
Bernard
B
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism*; D016923:Cell Death / Q000276:immunology; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008546:Melanoma, Experimental; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D030421:Peroxynitrous Acid / Q000633:toxicity*
D000951:Antigens, Neoplasm; D030421:Peroxynitrous Acid