| First Author | Pylayeva-Gupta Y | Year | 2016 |
| Journal | Cancer Discov | Volume | 6 |
| Issue | 3 | Pages | 247-55 |
| PubMed ID | 26715643 | Mgi Jnum | J:236131 |
| Mgi Id | MGI:5804752 | Doi | 10.1158/2159-8290.CD-15-0843 |
| Citation | Pylayeva-Gupta Y, et al. (2016) IL35-Producing B Cells Promote the Development of Pancreatic Neoplasia. Cancer Discov 6(3):247-55 |
| abstractText | 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 (muMT), 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. SIGNIFICANCE: 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. |
