Pyrolyzed deketene curcumin controls regulatory T cell generation and gastric cancer metabolism cooperate with

Takashi MaruYama1,2,3, Hirofumi Miyazaki3, Yun-Ji Lim1

  • 1Mucosal Immunology Section, National Institute of Dental and Craniofacial Research (NIDCR), National Institute of Health, Bethesda, MD, United States.

Frontiers in Immunology
|February 23, 2023
PubMed

Insights

Pyrolyzed deketene curcumin GO-Y022 inhibits gastric tumor growth by restricting glucose metabolism and promoting anti-tumor immunity. This compound reduces L-lactate production and Treg generation in gastric cancer cells.

Area of Science:

  • Immunology
  • Oncology
  • Biochemistry

Background:

  • Pyrolyzed deketene curcumin GO-Y022 demonstrates anti-carcinogenic effects in gastric cancer models.
  • The impact of GO-Y022 on tumor-induced immune suppression, particularly regulatory T cells (Tregs), remains unclear.

Purpose of the Study:

  • To investigate the effect of GO-Y022 on Treg generation in gastric cancer.
  • To elucidate the mechanisms by which gastric tumor cells modulate GO-Y022's anti-Treg activity.

Main Methods:

  • Investigated GO-Y022's effect on Treg generation in vitro with transforming growth factor beta 1 (TGF-β).
  • Analyzed L-lactate production by gastric tumor cells treated with GO-Y022.
  • Co-cultured naïve CD4+ T cells with GO-Y022 treated gastric tumor cells.
  • Assessed the impact of 2-deoxy-d-glucose (2DG), a glycolysis inhibitor, in combination with GO-Y022.

Main Results:

  • GO-Y022 inhibited Treg generation induced by TGF-β but had limited effect on established Foxp3+ Tregs in the tumor microenvironment.
  • Gastric tumor cells treated with GO-Y022 increased L-lactate production, counteracting GO-Y022's inhibitory effect on Treg generation.
  • Co-culture with GO-Y022 treated tumor cells enhanced Treg generation.
  • Combination treatment with GO-Y022 and 2DG reduced L-lactate production and Treg generation.
  • Combined therapy enhanced GO-Y022-induced tumor cell death.

Conclusions:

  • GO-Y022, when combined with restricted glucose metabolism (e.g., using 2DG), effectively inhibits gastric tumor cell survival.
  • This combined approach promotes anti-tumor immunity by reducing Treg generation and L-lactate production.