2024-03-28T23:44:59Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/777552022-11-17T02:08:08Zhdl_2115_20044hdl_2115_124Influence on [F-18]FDG uptake by cancer cells after anti-PD-1 therapy in an enforced-immune activated mouse tumorTomita, MayuSuzuki, MotofumiKono, YusukeNakajima, KoheiMatsuda, TakumaKuge, YujiOgawa, MikakoPD-1Immune checkpoint inhibitor[F-18]FDGcGAMP460Background Anti-programmed cell death 1 (PD-1) antibody is an immune checkpoint inhibitor, and anti-PD-1 therapy improves the anti-tumor functions of T cells and affects tumor microenvironment. We previously reported that anti-PD-1 treatment affected tumor glycolysis by using 2-deoxy-2-[F-18]fluoro-D-glucose ([F-18]FDG) positron emission tomography (PET). That study showed that anti-PD-1 therapy in a mouse B16F10 melanoma model increased glucose metabolism in cancer cells at the point where anti-PD-1 therapy did not cause a significant inhibition of tumor growth. However, the B16F10 melanoma model is poorly immunogenic, so it is not clear how anti-PD-1 treatment affects glucose metabolism in highly immunogenic cancer models. In this study, we used a cyclic dinucleotide GMP-AMP (cGAMP)-injected B16F10 melanoma model to investigate the effect of anti-PD-1 therapy on [F-18]FDG uptake in a highly immune activated tumor in mice. Results To compare the cGAMP-injected B16F10 model with the B16F10 model, experiments were performed as described in our previous manuscript. [F-18]FDG-PET was measured before treatment and 7 days after the start of treatment. In this study, [F-18]FDG uptake in tumors in the cGAMP/anti-PD-1 combination group was lower than that in the anti-PD-1 treatment group tumors on day 7, as shown by PET and ex vivo validation. Flow-cytometry was performed to assess immune cell populations and glucose metabolism. Anti-PD-1 and/or cGAMP treatment increased the infiltration level of immune cells into tumors. The cGAMP/anti-PD-1 combination group had significantly lower levels of GLUT1(high) cells/hexokinase IIhigh cells in CD45(-) cancer cells compared with tumors in the anti-PD-1 treated group. These results suggested that if immune responses in tumors are higher than a certain level, glucose uptake in cancer cells is reduced depending on that level. Such a change of glucose uptake might be caused by the difference in infiltration or activation level of immune cells between the anti-PD-1 treated group and the cGAMP/anti-PD-1 combination group. Conclusions [F-18]FDG uptake in cancer cells after anti-PD-1 treatment might be affected by the tumor immune microenvironment including immune cell infiltration, composition, and activation status.Springer (SpringerOpen)Journal Articlehttp://hdl.handle.net/2115/777552191-219XEJNMMI research101242020-03-19enginfo:doi/10.1186/s13550-020-0608-4none