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Amlexanox enhances the antitumor effect of anti-PD-1 antibody
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| Title: | Amlexanox enhances the antitumor effect of anti-PD-1 antibody |
| Authors: | Takeda, Kazuhiko Browse this author | | Yano, Koji Browse this author | | Yamada, Kaoru Browse this author | | Kihara, Akio Browse this author →KAKEN DB |
| Keywords: | Cancer | | Cancer immunotherapy | | Cytotoxic T cell | | Immunity | | Interferon-γ |
| Issue Date: | 30-Jun-2021 |
| Publisher: | Elsevier |
| Journal Title: | Biochemical and biophysical research communications |
| Volume: | 560 |
| Start Page: | 1 |
| End Page: | 6 |
| Publisher DOI: | 10.1016/j.bbrc.2021.04.126 |
| Abstract: | Cancer immunotherapy, especially treatment with monoclonal antibodies (mAbs) that block programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) signaling, has attracted attention as a new therapeutic option for cancer. However, only a limited number of patients have responded to this treatment approach. In this study, we searched for compounds that enhance the efficacy of anti-PD-1 mAb using mixed lymphocyte reaction (MLR), which is a mixed culture system of the two key cells (dendritic and T cells) involved in tumor immunity. We found that amlexanox enhanced production of interferon (IFN)-gamma, an indicator of T cell activation, by anti-PD-1 mAb. Amlexanox also induced PD-L1 expression in dendritic cells in MLR, whereas it did not stimulate interleukin-2 production by Jurkat T cells. These results suggest that amlexanox acts on dendritic cells, not T cells, in MLR. Furthermore, it enhanced the antitumor effect of the anti-PD-1 mAb in vivo in a mouse tumor-bearing model. The combination of amlexanox and anti-PD-1 mAb increased the expression of Ifng encoding IFN-gamma, IFN-gamma-related genes, Cd274 encoding PD-L1, and cytotoxic T cell-related genes in tumors. In conclusion, amlexanox stimulates the antitumor effect of anti-PD-1 mAb by acting on dendritic cells, which in turn activates cytotoxic T cells in tumors. |
| Rights: | © <2021>. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/86278 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 木原 章雄
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