Abstract
BackgroundProgrammed 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-[18F]fluoro-d-glucose ([18F]FDG) uptake in vivo, focusing on cell distribution and glycolysis in both cancer and immune cells.ResultsIn a B16F10 melanoma model, [18F]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 [18F]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 [18F]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.ConclusionThe present study shows that anti PD-1 therapy increases glucose metabolism in cancer cells.
Highlights
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
Tumor measurements were made two to three times weekly using calipers, and the volume was expressed in mm3 [0.5 × L × W2] (L, long diameters; W, short diameters of the tumor). [18F]FDG-positron emission tomography (PET)/Computed Tomography (CT) imaging was performed just prior to initiating therapy and at 7 days after the initiation of anti PD-1 treatment initiation (Fig. 1a)
PET-CT scans and mean/maximum [18F]FDG uptake values in tumors are shown in Fig. 1c, d
Summary
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. The interaction between programmed cell death 1 (PD-1) and its ligand 1 (PD-L1) is a mechanism involved in the ability of immunogenic tumors to escape the immune response. Blockade of this interaction activates autoimmunity towards the tumor and provides a strategy for tumor immunotherapy [1]. Immune checkpoint inhibitors target immune systems; interaction between immune and tumor cells is important for therapeutic effects. Molecular imaging technique (e.g., positron emission tomography; PET) should be helpful for evaluating the therapeutic effect
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