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The Curcumin Analog GO-Y030 Controls the Generation and Stability of Regulatory T Cells

Regulatory T cells (Tregs) play a crucial role in preventing antitumor immune responses in cancer tissues. Cancer tissues produce large amounts of transforming growth factor beta (TGF-β), which promotes the generation of Foxp3(+) Tregs from naïve CD4(+) T cells in the local tumor microenvironment. T...

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Detalles Bibliográficos
Autores principales: MaruYama, Takashi, Kobayashi, Shuhei, Nakatsukasa, Hiroko, Moritoki, Yuki, Taguchi, Daiki, Sunagawa, Yoichi, Morimoto, Tatsuya, Asao, Atsuko, Jin, Wenwen, Owada, Yuji, Ishii, Naoto, Iwabuchi, Yoshiharu, Yoshimura, Akihiko, Chen, WanJun, Shibata, Hiroyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261301/
https://www.ncbi.nlm.nih.gov/pubmed/34248973
http://dx.doi.org/10.3389/fimmu.2021.687669
Descripción
Sumario:Regulatory T cells (Tregs) play a crucial role in preventing antitumor immune responses in cancer tissues. Cancer tissues produce large amounts of transforming growth factor beta (TGF-β), which promotes the generation of Foxp3(+) Tregs from naïve CD4(+) T cells in the local tumor microenvironment. TGF-β activates nuclear factor kappa B (NF-κB)/p300 and SMAD signaling, which increases the number of acetylated histones at the Foxp3 locus and induces Foxp3 gene expression. TGF-β also helps stabilize Foxp3 expression. The curcumin analog and antitumor agent, GO-Y030, prevented the TGF-β-induced generation of Tregs by preventing p300 from accelerating NF-κB-induced Foxp3 expression. Moreover, the addition of GO-Y030 resulted in a significant reduction in the number of acetylated histones at the Foxp3 promoter and at the conserved noncoding sequence 1 regions that are generated in response to TGF-β. In vivo tumor models demonstrated that GO-Y030-treatment prevented tumor growth and reduced the Foxp3(+) Tregs population in tumor-infiltrating lymphocytes. Therefore, GO-Y030 exerts a potent anticancer effect by controlling Treg generation and stability.