Dectin 1 activation on macrophages by galectin 9 promotes pancreatic carcinoma and peritumoral immune tolerance.
| dc.contributor.author | Daley, Donnele | |
| dc.contributor.author | Mani, Vishnu R | |
| dc.contributor.author | Mohan, Navyatha | |
| dc.contributor.author | Akkad, Neha | |
| dc.contributor.author | Ochi, Atsuo | |
| dc.contributor.author | Heindel, Daniel W | |
| dc.contributor.author | Lee, Ki Buom | |
| dc.contributor.author | Zambirinis, Constantinos P | |
| dc.contributor.author | Pandian, Gautam Sd Balasubramania | |
| dc.contributor.author | Savadkar, Shivraj | |
| dc.contributor.author | Torres-Hernandez, Alejandro | |
| dc.contributor.author | Nayak, Shruti | |
| dc.contributor.author | Wang, Ding | |
| dc.contributor.author | Hundeyin, Mautin | |
| dc.contributor.author | Diskin, Brian | |
| dc.contributor.author | Aykut, Berk | |
| dc.contributor.author | Werba, Gregor | |
| dc.contributor.author | Barilla, Rocky M | |
| dc.contributor.author | Rodriguez, Robert | |
| dc.contributor.author | Chang, Steven | |
| dc.contributor.author | Gardner, Lawrence | |
| dc.contributor.author | Mahal, Lara K | |
| dc.contributor.author | Ueberheide, Beatrix | |
| dc.contributor.author | Miller, George | |
| dc.date.accessioned | 2024-02-23T20:16:14Z | |
| dc.date.available | 2024-02-23T20:16:14Z | |
| dc.date.issued | 2017-05 | |
| dc.description.abstract | The progression of pancreatic oncogenesis requires immune-suppressive inflammation in cooperation with oncogenic mutations. However, the drivers of intratumoral immune tolerance are uncertain. Dectin 1 is an innate immune receptor crucial for anti-fungal immunity, but its role in sterile inflammation and oncogenesis has not been well defined. Furthermore, non-pathogen-derived ligands for dectin 1 have not been characterized. We found that dectin 1 is highly expressed on macrophages in pancreatic ductal adenocarcinoma (PDA). Dectin 1 ligation accelerated the progression of PDA in mice, whereas deletion of Clec7a-the gene encoding dectin 1-or blockade of dectin 1 downstream signaling was protective. We found that dectin 1 can ligate the lectin galectin 9 in mouse and human PDA, which results in tolerogenic macrophage programming and adaptive immune suppression. Upon disruption of the dectin 1-galectin 9 axis, CD4+ and CD8+ T cells, which are dispensable for PDA progression in hosts with an intact signaling axis, become reprogrammed into indispensable mediators of anti-tumor immunity. These data suggest that targeting dectin 1 signaling is an attractive strategy for developing an immunotherapy for PDA. | |
| dc.identifier | nm.4314 | |
| dc.identifier.issn | 1078-8956 | |
| dc.identifier.issn | 1546-170X | |
| dc.identifier.uri | ||
| dc.language | eng | |
| dc.publisher | Springer Science and Business Media LLC | |
| dc.relation.ispartof | Nature medicine | |
| dc.relation.isversionof | 10.1038/nm.4314 | |
| dc.rights.uri | ||
| dc.subject | Pancreatic Ducts | |
| dc.subject | Epithelial Cells | |
| dc.subject | Animals | |
| dc.subject | Mice, Knockout | |
| dc.subject | Humans | |
| dc.subject | Mice | |
| dc.subject | Carcinoma, Pancreatic Ductal | |
| dc.subject | Pancreatic Neoplasms | |
| dc.subject | Lectins, C-Type | |
| dc.subject | Galectins | |
| dc.subject | Blotting, Western | |
| dc.subject | Flow Cytometry | |
| dc.subject | Immunohistochemistry | |
| dc.subject | Immunoprecipitation | |
| dc.subject | Immune Tolerance | |
| dc.subject | Tumor Escape | |
| dc.subject | Mass Spectrometry | |
| dc.subject | Gene Knockdown Techniques | |
| dc.subject | Carcinogenesis | |
| dc.subject | Syk Kinase | |
| dc.title | Dectin 1 activation on macrophages by galectin 9 promotes pancreatic carcinoma and peritumoral immune tolerance. | |
| dc.type | Journal article | |
| duke.contributor.orcid | Mani, Vishnu R|0000-0003-3121-9497 | |
| duke.contributor.orcid | Aykut, Berk|0000-0001-8343-4258 | |
| pubs.begin-page | 556 | |
| pubs.end-page | 567 | |
| pubs.issue | 5 | |
| pubs.organisational-group | Duke | |
| pubs.organisational-group | School of Medicine | |
| pubs.organisational-group | Staff | |
| pubs.organisational-group | Clinical Science Departments | |
| pubs.organisational-group | Surgery | |
| pubs.publication-status | Published | |
| pubs.volume | 23 |
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