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Anti PD-1 treatment increases [F-18]FDG uptake by cancer cells in a mouse B16F10 melanoma model
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| Title: | Anti PD-1 treatment increases [F-18]FDG uptake by cancer cells in a mouse B16F10 melanoma model |
| Authors: | Tomita, Mayu Browse this author | | Yasui, Hironobu Browse this author | | Higashikawa, Kei Browse this author | | Nakajima, Kohei Browse this author | | Takakura, Hideo Browse this author | | Shiga, Tohru Browse this author | | Kuge, Yuji Browse this author | | Ogawa, Mikako Browse this author →KAKEN DB |
| Keywords: | PD-1 | | Immune checkpoint inhibitor | | [F-18]FDG | | Tumor microenvironment | | Mouse melanoma |
| Issue Date: | 16-Aug-2018 |
| Publisher: | Springer (SpringerOpen) |
| Journal Title: | EJNMMI research |
| Volume: | 8 |
| Start Page: | 82 |
| Publisher DOI: | 10.1186/s13550-018-0433-1 |
| Abstract: | Background: Programmed cell death 1 (PD-1) inhibitors act as immune checkpoint inhibitors and are more effective for improving survival time with less toxicity as compared with conventional chemotherapies. In anti PD-1 therapy, it is important to evaluate metabolism in the cancer microenvironment, as this helps to clarify the pathological conditions. Herein, we investigate the early effects of PD-1 therapy on 2-deoxy-2-[F-18]fluoro-D-glucose ([F-18]FDG) uptake in vivo, focusing on cell distribution and glycolysis in both cancer and immune cells. Results: In a B16F10 melanoma model, [F-18]FDG-positron emission tomography (PET) was performed before treatment and 7 days after the start of treatment. Values were calculated as the percentage-injected activity per gram of tissue (%IA/g). Flow-cytometry was then performed to assess immune cell populations and glucose metabolism. There was a negligible difference in [18F]FDG uptake between tumors in the treatment group and non-treatment group before the treatment. In contrast, mean [F-18]FDG uptake in the treatment group tumors was significantly higher (8.06 +/- 0.48 %IA/g; P= 0.0074) than that in the non-treatment group (4.02 +/- 1.03 %IA/g) after anti PD-1 treatment. Assessment of tumor immune cell populations showed that treatment slightly enriched CD8(+) T cells and CD4(+) T cells; however, infiltration of immune cells was negligible, and thus, immune cells were not responsible for the increase in [F-18]FDG uptake. On the other hand, anti PD-1 treatment significantly increased glucose transporter 1 (GLUT1) and hexokinase II expression in CD45(-) cancer cells, indicating that anti PD-1 treatment increased glucose metabolism in cancer cells. Conclusion: The present study shows that anti PD-1 therapy increases glucose metabolism in cancer cells. |
| Rights: | http://creativecommons.org/licenses/by/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/71528 |
| 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: 小川 美香子
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