title: IL35-Producing B Cells Promote the Development of Pancreatic Neoplasia.
abstract: A salient feature of pancreatic ductal adenocarcinoma (PDAC) is an abundant fibroinflammatory response characterized by the recruitment of immune and mesenchymal cells and the consequent establishment of a protumorigenic microenvironment. Here, we report the prominent presence of B cells in human pancreatic intraepithelial neoplasia and PDAC lesions as well as in oncogenic Kras-driven pancreatic neoplasms in the mouse. The growth of orthotopic pancreatic neoplasms harboring oncogenic Kras was significantly compromised in B-cell-deficient mice (μMT), and this growth deficiency could be rescued by the reconstitution of a CD1d(hi)CD5(+) B-cell subset. The protumorigenic effect of B cells was mediated by their expression of IL35 through a mechanism involving IL35-mediated stimulation of tumor cell proliferation. Our results identify a previously unrecognized role for IL35-producing CD1d(hi)CD5(+) B cells in the pathogenesis of pancreatic cancer and underscore the potential significance of a B-cell/IL35 axis as a therapeutic target.
  
  
  CONCLUSIONS
  This study identifies a B-cell subpopulation that accumulates in the pancreatic parenchyma during early neoplasia and is required to support tumor cell growth. Our findings provide a rationale for exploring B-cell-based targeting approaches for the treatment of pancreatic cancer.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York.
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Pylayeva-Gupta
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York.
authors.forename: Shipra
authors.initials: S
authors.lastname: Das
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York.
authors.forename: Jesse S
authors.initials: JS
authors.lastname: Handler
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, New York.
authors.forename: Cristina H
authors.initials: CH
authors.lastname: Hajdu
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, New York.
authors.forename: Maryaline
authors.initials: M
authors.lastname: Coffre
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, New York.
authors.forename: Sergei B
authors.initials: SB
authors.lastname: Koralov
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York. Dafna.Bar-Sagi@med.nyu.edu.
authors.forename: Dafna
authors.initials: D
authors.lastname: Bar-Sagi
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D015415:Biomarkers; D021441:Carcinoma, Pancreatic Ductal; D002471:Cell Transformation, Neoplastic / Q000276:immunology* / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D007378:Interleukins / Q000096:biosynthesis*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype
chemical_list: D015415:Biomarkers; D007378:Interleukins; C532417:interleukin-35, human