|
Hokkaido University Collection of Scholarly and Academic Papers >
Institute for Genetic Medicine >
Peer-reviewed Journal Articles, etc >
Interleukin-34 Limits the Therapeutic Effects of Immune Checkpoint Blockade
This item is licensed under:Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
| Title: | Interleukin-34 Limits the Therapeutic Effects of Immune Checkpoint Blockade |
| Authors: | Hama, Naoki Browse this author | | Kobayashi, Takuto Browse this author | | Han, Nanumi Browse this author | | Kitagawa, Fumihito Browse this author | | Kajihara, Nabeel Browse this author | | Otsuka, Ryo Browse this author | | Wada, Haruka Browse this author →KAKEN DB | | Lee, Hee-kyung Browse this author | | Rhee, Hwanseok Browse this author | | Hasegawa, Yoshinori Browse this author | | Yagita, Hideo Browse this author | | Baghdadi, Muhammad Browse this author →KAKEN DB | | Seino, Ken-ichiro Browse this author →KAKEN DB |
| Issue Date: | 23-Oct-2020 |
| Publisher: | Cell Press |
| Journal Title: | iScience |
| Volume: | 23 |
| Issue: | 10 |
| Start Page: | 101584 |
| Publisher DOI: | 10.1016/j.isci.2020.101584 |
| Abstract: | Interleukin-34 (IL-34) is an alternative ligand to colony-stimulating factor-1 (CSF-1) for the CSF-1 receptor that acts as a key regulator of monocyte/macrophage lineage. In this study, we show that tumor-derived IL-34 mediates resistance to immune checkpoint blockade regardless of CSF-1 existence in variousmurine cancer models. Consistent with its immunosuppressive characteristics, the expression of IL-34 in tumors correlates with decreased frequencies of cellular (such as CD8(+) and CD4(+) T cells and M1-biased macrophages) and molecular (including various cytokines and chemokines) effectors at the tumor microenvironment. Then, a neutralizing antibody against IL-34 improved the therapeutic effects of the immune checkpoint blockade in combinatorial therapeutic models, including a patient-derived xenograft model. Collectively, we revealed that tumor-derived IL-34 inhibits the efficacy of immune checkpoint blockade and proposed the utility of IL-34 blockade as a new strategy for cancer therapy. |
| Rights: | https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/80267 |
| 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)
|
|
