4.8 Article

Pyrolyzed deketene curcumin controls regulatory T cell generation and gastric cancer metabolism cooperate with 2-deoxy-d-glucose

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FRONTIERS IN IMMUNOLOGY
卷 14, 期 -, 页码 -

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FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2023.1049713

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tumor microenvironment; stomach neoplasms; adenosine triphosphate; glycolysis; regulatory T cells

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Pyrolyzed deketene curcumin GO-Y022 prevents carcinogenesis in a gastric cancer mouse model, but its effect on tumor-induced immune suppression is still unclear. In this study, it was found that GO-Y022 inhibited Treg generation in the presence of transforming growth factor beta 1 (TGF-beta). However, GO-Y022 had limited impact on Foxp3(+) Tregs in the gastric tumor microenvironment. Gastric tumor cells produced a large amount of L-lactate in the presence of GO-Y022, which undermined the inhibitory effect of GO-Y022 on Treg generation in response to TGF-beta. Combination treatment with GO-Y022 and 2-deoxy-d-glucose (2DG) reduced L-lactate production and Treg generation in gastric tumor cells, leading to inhibition of gastric tumor cell survival and promotion of anti-tumor immunity.
Pyrolyzed deketene curcumin GO-Y022 prevents carcinogenesis in a gastric cancer mouse model. However, it is still less clear if GO-Y022 affects tumor-induced immune suppression. In this study, we found that GO-Y022 inhibited Treg generation in the presence of transforming growth factor beta 1 (TGF-beta). However, GO-Y022 showed less impact on Foxp3(+) Tregs in the gastric tumor microenvironment. Gastric tumor cells produce a large amount of L-lactate in the presence of GO-Y022 and diminish the inhibitory role of GO-Y022 against Treg generation in response to TGF-beta. Therefore, naive CD4(+) T cells co-cultured with GO-Y022 treated gastric tumor cells increased Treg generation. GO-Y022-induced tumor cell death was further enhanced by 2-deoxy-d-glucose (2DG), a glycolysis inhibitor. Combination treatment of GO-Y022 and 2DG results in reduced L-lactate production and Treg generation in gastric tumor cells. Overall, GO-Y022-treatment with restricted glucose metabolism inhibits gastric tumor cell survival and promotes anti-tumor immunity.

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