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]fluoro-D-glucose ([F]FDG) uptake in vivo, focusing on cell distribution and glycolysis in both cancer and immune cells.

RESULTS

In a B16F10 melanoma model, [F]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 [F]FDG uptake between tumors in the treatment group and non-treatment group before the treatment. In contrast, mean [F]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]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.