A novel dendritic cell subset involved in tumor immunosurveillance.
The interferon (IFN)-gamma-induced TRAIL effector mechanism is a vital component of cancer immunosurveillance by natural killer (NK) cells in mice. Here we show that the main source of IFN-gamma is not the conventional NK cell but a subset of B220(+)Ly6C(-) dendritic cells, which are atypical insofar as they express NK cell-surface molecules. Upon contact with a variety of tumor cells that are poorly recognized by NK cells, B220(+)NK1.1(+) dendritic cells secrete high levels of IFN-gamma and mediate TRAIL-dependent lysis of tumor cells. Adoptive transfer of these IFN-producing killer dendritic cells (IKDCs) into tumor-bearing Rag2(-/-)Il2rg(-/-) mice prevented tumor outgrowth, whereas transfer of conventional NK cells did not. In conclusion, we identified IKDCs as pivotal sensors and effectors of the innate antitumor immune response.
Taieb
Julien
J
ERM0208 INSERM, Faculté de Médecine Kremlin Bicêtre, Institut Gustave Roussy, Villejuif, France.
Chaput
Nathalie
N
Ménard
Cédric
C
Apetoh
Lionel
L
Ullrich
Evelyn
E
Bonmort
Mathieu
M
Péquignot
Marie
M
Casares
Noelia
N
Terme
Magali
M
Flament
Caroline
C
Opolon
Paule
P
Lecluse
Yann
Y
Métivier
Didier
D
Tomasello
Elena
E
Vivier
Eric
E
Ghiringhelli
François
F
Martin
François
F
Klatzmann
David
D
Poynard
Thierry
T
Tursz
Thomas
T
Raposo
Graça
G
Yagita
Hideo
H
Ryffel
Bernard
B
Kroemer
Guido
G
Zitvogel
Laurence
L
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D000950:Antigens, Ly; D000954:Antigens, Surface / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000276:immunology; D039521:CD11c Antigen / Q000378:metabolism; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D003713:Dendritic Cells / Q000145:classification* / Q000276:immunology* / Q000648:ultrastructure; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D053631:Interleukin Receptor Common gamma Subunit; D007694:Killer Cells, Natural / Q000276:immunology; D037181:Lectins, C-Type / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D008854:Microscopy, Electron; D055651:NK Cell Lectin-Like Receptor Subfamily B; D009374:Neoplasms, Experimental / Q000276:immunology*; D018123:Receptors, Interleukin / Q000172:deficiency / Q000235:genetics; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000950:Antigens, Ly; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D039521:CD11c Antigen; D004268:DNA-Binding Proteins; C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D055651:NK Cell Lectin-Like Receptor Subfamily B; C499308:Rag2 protein, mouse; D018123:Receptors, Interleukin; D053221:TNF-Related Apoptosis-Inducing Ligand; C505654:Tnfsf10 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens