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Influence on [F-18]FDG uptake by cancer cells after anti-PD-1 therapy in an enforced-immune activated mouse tumor

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Title: Influence on [F-18]FDG uptake by cancer cells after anti-PD-1 therapy in an enforced-immune activated mouse tumor
Authors: Tomita, Mayu Browse this author
Suzuki, Motofumi Browse this author →KAKEN DB
Kono, Yusuke Browse this author
Nakajima, Kohei Browse this author
Matsuda, Takuma Browse this author
Kuge, Yuji Browse this author
Ogawa, Mikako Browse this author →KAKEN DB
Keywords: PD-1
Immune checkpoint inhibitor
[F-18]FDG
cGAMP
Issue Date: 19-Mar-2020
Publisher: Springer (SpringerOpen)
Journal Title: EJNMMI research
Volume: 10
Issue: 1
Start Page: 24
Publisher DOI: 10.1186/s13550-020-0608-4
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-[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.
Type: article
URI: http://hdl.handle.net/2115/77755
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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