| Title: | Chemotherapy-Derived Inflammatory Responses Accelerate the Formation of Immunosuppressive Myeloid Cells in the Tissue Microenvironment of Human Pancreatic Cancer |
| Authors: | Takeuchi, Shintaro Browse this author |
| Baghdadi, Muhammad Browse this author |
| Tsuchikawa, Takahiro Browse this author →KAKEN DB |
| Wada, Haruka Browse this author →KAKEN DB |
| Nakamura, Toru Browse this author →KAKEN DB |
| Abe, Hirotake Browse this author |
| Nakanishi, Sayaka Browse this author |
| Usui, Yuu Browse this author |
| Higuchi, Kohtaro Browse this author |
| Takahashi, Mizuna Browse this author |
| Inoko, Kazuho Browse this author |
| Sato, Syoki Browse this author |
| Takano, Hironobu Browse this author |
| Shichinohe, Toshiaki Browse this author →KAKEN DB |
| Seino, Ken-ichiro Browse this author →KAKEN DB |
| Hirano, Satoshi Browse this author →KAKEN DB |
| Issue Date: | 1-Jul-2015 |
| Publisher: | American Association for Cancer Research (AACR) |
| Journal Title: | Cancer research |
| Volume: | 75 |
| Issue: | 13 |
| Start Page: | 2629 |
| End Page: | 2640 |
| Publisher DOI: | 10.1158/0008-5472.CAN-14-2921 |
| PMID: | 25952647 |
| Abstract: | Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic malignancies. PDAC builds a tumor microenvironment that plays critical roles in tumor progression and metastasis. However, the relationship between chemotherapy and modulation of PDAC-induced tumor microenvironment remains poorly understood. In this study, we report a role of chemotherapy-derived inflammatory response in the enrichment of PDAC microenvironment with immunosuppressive myeloid cells. Granulocyte macrophage colony-stimulating factor (GM-CSF) is a major cytokine associated with oncogenic KRAS in PDAC cells. GM-CSF production was significantly enhanced in various PDAC cell lines or PDAC tumor tissues from patients after treatment with chemotherapy, which induced the differentiation of monocytes into myeloid-derived suppressor cells (MDSC). Furthermore, blockade of GM-CSF with monoclonal antibodies helped to restore T-cell proliferation when cocultured with monocytes stimulated with tumor supernatants. GM-CSF expression was also observed in primary tumors and correlated with poor prognosis in PDAC patients. Together, these results describe a role of GM-CSF in the modification of chemotherapy-treated PDAC microenvironment and suggest that the targeting of GM-CSF may benefit PDAC patients' refractory to current anticancer regimens by defeating MDSC-mediated immune escape. |
| Description: | Supplementary data for this article are available at Cancer Research Online |
| Description URI: | http://cancerres.aacrjournals.org/content/75/13/2629.figures-only |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/62325 |
| Appears in Collections: | 遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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