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热解双烯酮姜黄素控制调节性 T 细胞的生成，与 2-脱氧-D-葡萄糖协同作用调控胃癌代谢。

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

机构信息

Mucosal Immunology Section, National Institute of Dental and Craniofacial Research (NIDCR), National Institute of Health, Bethesda, MD, United States.

Department of Immunology, Graduate School of Medicine, Akita University, Akita, Japan.

出版信息

Front Immunol. 2023 Feb 6;14:1049713. doi: 10.3389/fimmu.2023.1049713. eCollection 2023.

DOI:10.3389/fimmu.2023.1049713
PMID:36814928
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9939626/
Abstract

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-β). 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-β. Therefore, naïve 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.

摘要

热解双烯酮姜黄素 GO-Y022 可预防胃癌小鼠模型中的癌变。然而，GO-Y022 是否影响肿瘤诱导的免疫抑制仍然不太清楚。在这项研究中，我们发现 GO-Y022 在转化生长因子β 1（TGF-β）存在的情况下抑制 Treg 的产生。然而，GO-Y022 在胃肿瘤微环境中对 Foxp3 Tregs 的影响较小。在存在 GO-Y022 的情况下，胃肿瘤细胞产生大量 L-乳酸，并减弱 GO-Y022 对 TGF-β诱导的 Treg 产生的抑制作用。因此，与用 GO-Y022 处理的胃肿瘤细胞共培养的幼稚 CD4 T 细胞增加了 Treg 的产生。葡萄糖代谢抑制剂 2-脱氧-D-葡萄糖（2DG）进一步增强了 GO-Y022 诱导的肿瘤细胞死亡。GO-Y022 和 2DG 的联合治疗可减少胃肿瘤细胞中 L-乳酸的产生和 Treg 的产生。总的来说，限制葡萄糖代谢的 GO-Y022 治疗可抑制胃肿瘤细胞的存活并促进抗肿瘤免疫。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d3d/9939626/af6eacf3d71c/fimmu-14-1049713-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d3d/9939626/a7633dff0a0a/fimmu-14-1049713-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d3d/9939626/4399dbd67ab7/fimmu-14-1049713-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d3d/9939626/dd4fd3c77ed2/fimmu-14-1049713-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d3d/9939626/f1066f01f600/fimmu-14-1049713-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d3d/9939626/af6eacf3d71c/fimmu-14-1049713-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d3d/9939626/a7633dff0a0a/fimmu-14-1049713-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d3d/9939626/f2d529738793/fimmu-14-1049713-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d3d/9939626/f98f20fb4e78/fimmu-14-1049713-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d3d/9939626/4399dbd67ab7/fimmu-14-1049713-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d3d/9939626/dd4fd3c77ed2/fimmu-14-1049713-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d3d/9939626/f1066f01f600/fimmu-14-1049713-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d3d/9939626/af6eacf3d71c/fimmu-14-1049713-g007.jpg

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