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Specialized dendritic cells induce tumor-promoting IL-10+IL-17+ FoxP3neg regulatory CD4+ T cells in pancreatic carcinoma.
Barilla, Rocky M; Diskin, Brian; Caso, Raul Caso; Lee, Ki Buom; Mohan, Navyatha; Buttar, Chandan; Adam, Salma; Sekendiz, Zennur; Wang, Junjie; Salas, Ruben D; Cassini, Marcelo F; Karlen, Jason; Sundberg, Belen; Akbar, Hashem; Levchenko, Dmitry; Gakhal, Inderdeep; Gutierrez, Johana; Wang, Wei; Hundeyin, Mautin; Torres-Hernandez, Alejandro; Leinwand, Joshua; Kurz, Emma; Rossi, Juan A Kochen; Mishra, Ankita; Liria, Miguel; Sanchez, Gustavo; Panta, Jyoti; Loke, P'ng; Aykut, Berk; Miller, George.
Afiliação
  • Barilla RM; S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
  • Diskin B; S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
  • Caso RC; S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
  • Lee KB; S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
  • Mohan N; S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
  • Buttar C; S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
  • Adam S; S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
  • Sekendiz Z; S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
  • Wang J; S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
  • Salas RD; S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
  • Cassini MF; S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
  • Karlen J; S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
  • Sundberg B; S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
  • Akbar H; S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
  • Levchenko D; S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
  • Gakhal I; S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
  • Gutierrez J; S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
  • Wang W; S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
  • Hundeyin M; S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
  • Torres-Hernandez A; S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
  • Leinwand J; S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
  • Kurz E; S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
  • Rossi JAK; S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
  • Mishra A; S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
  • Liria M; S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
  • Sanchez G; S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
  • Panta J; Department of Microbiology, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
  • Loke P; Department of Microbiology, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
  • Aykut B; S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
  • Miller G; S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA. george.miller@nyumc.org.
Nat Commun ; 10(1): 1424, 2019 03 29.
Article em En | MEDLINE | ID: mdl-30926808
ABSTRACT
The drivers and the specification of CD4+ T cell differentiation in the tumor microenvironment and their contributions to tumor immunity or tolerance are incompletely understood. Using models of pancreatic ductal adenocarcinoma (PDA), we show that a distinct subset of tumor-infiltrating dendritic cells (DC) promotes PDA growth by directing a unique TH-program. Specifically, CD11b+CD103- DC predominate in PDA, express high IL-23 and TGF-ß, and induce FoxP3neg tumor-promoting IL-10+IL-17+IFNγ+ regulatory CD4+ T cells. The balance between this distinctive TH program and canonical FoxP3+ TREGS is unaffected by pattern recognition receptor ligation and is modulated by DC expression of retinoic acid. This TH-signature is mimicked in human PDA where it is associated with immune-tolerance and diminished patient survival. Our data suggest that CD11b+CD103- DC promote CD4+ T cell tolerance in PDA which may underscore its resistance to immunotherapy.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Células Dendríticas / Interleucina-10 / Linfócitos T Reguladores / Interleucina-17 Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Células Dendríticas / Interleucina-10 / Linfócitos T Reguladores / Interleucina-17 Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos