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

作者：Tomita Mayu; Yasui Hironobu; Higashikawa Kei; Nakajima Kohei; Takakura Hideo; Shiga Tohru; Kuge Yuji; Ogawa Mikako^*

来源：EJNMMI Research, 2018, 8(1): 82.

DOI：10.1186/s13550-018-0433-1

• PD-1
• Immune checkpoint inhibitor
• [F-18]FDG
• Tumor microenvironment
• Mouse melanoma

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.

• 出版日期2018-8-16