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Interleukin-34 Limits the Therapeutic Effects of Immune Checkpoint Blockade

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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.
Type: article
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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