Influence on [18F]FDG uptake by cancer cells after anti-PD-1 therapy in an enforced-immune activated mouse tumor
Abstract Background 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-[18F...
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| Format: | Article |
| Language: | English |
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SpringerOpen
2020-03-01
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| Series: | EJNMMI Research |
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| Online Access: | http://link.springer.com/article/10.1186/s13550-020-0608-4 |
| _version_ | 1818205071522922496 |
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| author | Mayu Tomita Motofumi Suzuki Yusuke Kono Kohei Nakajima Takuma Matsuda Yuji Kuge Mikako Ogawa |
| author_facet | Mayu Tomita Motofumi Suzuki Yusuke Kono Kohei Nakajima Takuma Matsuda Yuji Kuge Mikako Ogawa |
| author_sort | Mayu Tomita |
| collection | DOAJ |
| description | Abstract Background 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-[18F]fluoro-D-glucose ([18F]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 [18F]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. [18F]FDG-PET was measured before treatment and 7 days after the start of treatment. In this study, [18F]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 GLUT1high 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 [18F]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. |
| first_indexed | 2024-12-12T03:51:18Z |
| format | Article |
| id | doaj.art-430db2dc891b40f0911dc39209ebe171 |
| institution | Directory Open Access Journal |
| issn | 2191-219X |
| language | English |
| last_indexed | 2024-12-12T03:51:18Z |
| publishDate | 2020-03-01 |
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| spelling | doaj.art-430db2dc891b40f0911dc39209ebe1712022-12-22T00:39:23ZengSpringerOpenEJNMMI Research2191-219X2020-03-0110111010.1186/s13550-020-0608-4Influence on [18F]FDG uptake by cancer cells after anti-PD-1 therapy in an enforced-immune activated mouse tumorMayu Tomita0Motofumi Suzuki1Yusuke Kono2Kohei Nakajima3Takuma Matsuda4Yuji Kuge5Mikako Ogawa6Laboratory of Bioanalysis and Molecular Imaging, Graduate School of Pharmaceutical Sciences, Hokkaido UniversityLaboratory of Bioanalysis and Molecular Imaging, Graduate School of Pharmaceutical Sciences, Hokkaido UniversityLaboratory of Bioanalysis and Molecular Imaging, Graduate School of Pharmaceutical Sciences, Hokkaido UniversityLaboratory of Bioanalysis and Molecular Imaging, Graduate School of Pharmaceutical Sciences, Hokkaido UniversityLaboratory of Bioanalysis and Molecular Imaging, Graduate School of Pharmaceutical Sciences, Hokkaido UniversityCentral Institute of Isotope Science, Hokkaido UniversityLaboratory of Bioanalysis and Molecular Imaging, Graduate School of Pharmaceutical Sciences, Hokkaido UniversityAbstract Background 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-[18F]fluoro-D-glucose ([18F]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 [18F]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. [18F]FDG-PET was measured before treatment and 7 days after the start of treatment. In this study, [18F]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 GLUT1high 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 [18F]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.http://link.springer.com/article/10.1186/s13550-020-0608-4PD-1Immune checkpoint inhibitor[18F]FDGcGAMP |
| spellingShingle | Mayu Tomita Motofumi Suzuki Yusuke Kono Kohei Nakajima Takuma Matsuda Yuji Kuge Mikako Ogawa Influence on [18F]FDG uptake by cancer cells after anti-PD-1 therapy in an enforced-immune activated mouse tumor EJNMMI Research PD-1 Immune checkpoint inhibitor [18F]FDG cGAMP |
| title | Influence on [18F]FDG uptake by cancer cells after anti-PD-1 therapy in an enforced-immune activated mouse tumor |
| title_full | Influence on [18F]FDG uptake by cancer cells after anti-PD-1 therapy in an enforced-immune activated mouse tumor |
| title_fullStr | Influence on [18F]FDG uptake by cancer cells after anti-PD-1 therapy in an enforced-immune activated mouse tumor |
| title_full_unstemmed | Influence on [18F]FDG uptake by cancer cells after anti-PD-1 therapy in an enforced-immune activated mouse tumor |
| title_short | Influence on [18F]FDG uptake by cancer cells after anti-PD-1 therapy in an enforced-immune activated mouse tumor |
| title_sort | influence on 18f fdg uptake by cancer cells after anti pd 1 therapy in an enforced immune activated mouse tumor |
| topic | PD-1 Immune checkpoint inhibitor [18F]FDG cGAMP |
| url | http://link.springer.com/article/10.1186/s13550-020-0608-4 |
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