The metastasis-associated immune response in pancreatic cancer : pathogenic role for a discrete dendritic cell population
Abstract/Contents
- Abstract
- Presentation with advanced disease and distant recurrence following surgery typify pancreatic ductal adenocarcinoma (PDAC), underscoring the need for new treatments targeting metastasis in this cancer. Because elements of the immune system can both prevent and promote tumor progression, we studied the metastasis-associated immune response in PDAC models. We find that developing metastases are bordered by dense networks of CD11b+ dendritic cells (DC), which derive from monocytes exposed to tumor-released GM-CSF and drive Foxp3+ T regulatory cell (Treg) responses. Leveraging their selective expression of the C-type lectin MGL2, we show that depleting this DC population from metastatic tissues activates cytotoxic lymphocytes, reduces Tregs, and inhibits metastasis development. These DC also uniquely express PD-L2 in the metastatic microenvironment and thereby inhibit CD8 T cell-mediated antitumor immunity. Similar DC accumulate in PDAC tissues from other models and cancer patients, supporting the broad applicability of our findings. These results reveal that a specific DC subset both suppresses CD8 T cells and supports Tregs to create a microenvironment conducive to metastasis in pancreatic cancer. Targeting such immunosuppressive stromal cells represents a novel strategy for preventing the progression of this deadly disease.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2014 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Kenkel, Justin Alan | |
|---|---|---|
| Associated with | Stanford University, Program in Immunology. | |
| Primary advisor | Engleman, Edgar G | |
| Thesis advisor | Engleman, Edgar G | |
| Thesis advisor | Contag, Christopher H | |
| Thesis advisor | Giaccia, Amato J | |
| Thesis advisor | Strober, Samuel | |
| Advisor | Contag, Christopher H | |
| Advisor | Giaccia, Amato J | |
| Advisor | Strober, Samuel |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Justin Alan Kenkel. |
|---|---|
| Note | Submitted to the Program in Immunology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2014. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2014 by Justin Alan Kenkel
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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