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

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

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.

Keywords: adenosine triphosphate; glycolysis; regulatory T cells; stomach neoplasms; tumor microenvironment.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Curcumin*
  • Deoxyglucose / metabolism
  • Glucose / metabolism
  • Mice
  • Stomach Neoplasms*
  • T-Lymphocytes, Regulatory
  • Tumor Microenvironment

Substances

  • Curcumin
  • Glucose
  • Deoxyglucose

Grants and funding

This research was supported in part by the Intramural Research Program of NIDCR, NIH to WC, and a Grant-in-Aid for Scientific Research (C) (20K11643) to HS.