Anti PD-1 treatment increases [F-18]FDG uptake by cancer cells in a mouse B16F10 melanoma model

Tomita, Mayu; Yasui, Hironobu; Higashikawa, Kei; Nakajima, Kohei; Takakura, Hideo; Shiga, Tohru; Kuge, Yuji; Ogawa, Mikako

Anti PD-1 treatment increases [F-18]FDG uptake by cancer cells in a mouse B16F10 melanoma model

Tomita, Mayu; Yasui, Hironobu; Higashikawa, Kei et al.

EJNMMI research, 2018, 8, 82

Permalink : https://hdl.handle.net/2115/71528

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アクセス権	open access
URI	https://hdl.handle.net/2115/71528
タイトル	Anti PD-1 treatment increases [F-18]FDG uptake by cancer cells in a mouse B16F10 melanoma model
著者	Tomita, Mayu ; Yasui, Hironobu ; Higashikawa, Kei ; Nakajima, Kohei ; Takakura, Hideo ; Shiga, Tohru ; Kuge, Yuji ; Ogawa, Mikako
著者名 Tomita, Mayu
著者名 Yasui, Hironobu
著者名 Higashikawa, Kei
著者名 Nakajima, Kohei
著者名 Takakura, Hideo
著者名 Shiga, Tohru
著者名 Kuge, Yuji
e-Rad_Researcher 20344351 著者名 Ogawa, Mikako
言語	英語
キーワード	PD-1
	Immune checkpoint inhibitor
	[F-18]FDG
	Tumor microenvironment
	Mouse melanoma
発行日	2018-08-16
出版者	Springer (SpringerOpen)
収録物名	EJNMMI research
巻(号)	8
ページ	82
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution 4.0 International
PISSN	2191-219X
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1186/s13550-018-0433-1