T Lymphocyte Inhibition by Tumor-Infiltrating Dendritic Cells Involves Ectonucleotidase CD39 but Not Arginase-1.
T lymphocytes activated by dendritic cells (DC) which present tumor antigens play a key role in the antitumor immune response. However, in patients suffering from active cancer, DC are not efficient at initiating and supporting immune responses as they participate to T lymphocyte inhibition. DC in the tumor environment are functionally defective and exhibit a characteristic of immature phenotype, different to that of DC present in nonpathological conditions. The mechanistic bases underlying DC dysfunction in cancer responsible for the modulation of T-cell responses and tumor immune escape are still being investigated. Using two different mouse tumor models, we showed that tumor-infiltrating DC (TIDC) are constitutively immunosuppressive, exhibit a semimature phenotype, and impair responder T lymphocyte proliferation and activation by a mechanism involving CD39 ectoenzyme.
INSERM UMR1098, University of Bourgogne Franche-Comté, EFS Bourgogne Franche-Comté, 25020 Besançon, France.
Malika
M
Trad
INSERM UMR1098, University of Bourgogne Franche-Comté, EFS Bourgogne Franche-Comté, 25020 Besançon, France.
Alexandrine
A
Gautheron
INSERM UMR1098, University of Bourgogne Franche-Comté, EFS Bourgogne Franche-Comté, 25020 Besançon, France.
Jennifer
J
Fraszczak
Department of Pediatrics, Steele Children's Research Center, Department of Immunobiology, BIO5 Institute and Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA.
Darya
D
Alizadeh
Department of Pediatrics, Steele Children's Research Center, Department of Immunobiology, BIO5 Institute and Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA.
Claire
C
Larmonier
Department of Pediatrics, Steele Children's Research Center, Department of Immunobiology, BIO5 Institute and Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA.
Collin J
CJ
LaCasse
Department of Pediatrics, Steele Children's Research Center, Department of Immunobiology, BIO5 Institute and Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA.
Sara
S
Centuori
INSERM UMR1098, University of Bourgogne Franche-Comté, EFS Bourgogne Franche-Comté, 25020 Besançon, France.
Sylvain
S
Audia
INSERM UMR1098, University of Bourgogne Franche-Comté, EFS Bourgogne Franche-Comté, 25020 Besançon, France.
Maxime
M
Samson
INSERM UMR1098, University of Bourgogne Franche-Comté, EFS Bourgogne Franche-Comté, 25020 Besançon, France.
Marion
M
Ciudad
INSERM UMR1098, University of Bourgogne Franche-Comté, EFS Bourgogne Franche-Comté, 25020 Besançon, France.
Francis
F
Bonnefoy
INSERM UMR866, University of Bourgogne Franche-Comté, 21000 Dijon, France.
Stéphanie
S
Lemaire-Ewing
Department of Pediatrics, Steele Children's Research Center, Department of Immunobiology, BIO5 Institute and Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA.
Emmanuel
E
Katsanis
INSERM UMR1098, University of Bourgogne Franche-Comté, EFS Bourgogne Franche-Comté, 25020 Besançon, France.
Sylvain
S
Perruche
INSERM UMR1098, University of Bourgogne Franche-Comté, EFS Bourgogne Franche-Comté, 25020 Besançon, France.
Philippe
P
Saas
INSERM UMR1098, University of Bourgogne Franche-Comté, EFS Bourgogne Franche-Comté, 25020 Besançon, France.
Bernard
B
Bonnotte
D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D001081:Apyrase / Q000276:immunology*; D001119:Arginase / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D019139:Tumor Escape
D015703:Antigens, CD; C544448:Arg1 protein, mouse; D001119:Arginase; D001081:Apyrase; C067869:CD39 antigen