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Curcumin analog GO‐Y030 boosts the efficacy of anti‐PD‐1 cancer immunotherapy

Regulatory T cells (Tregs) in the tumor microenvironment regulate tumor immunity. Programmed cell death protein 1 (PD‐1) is known to be expressed on Tregs and plays crucial roles in suppressing tumor immunity. However, the immune checkpoint inhibitor, anti‐PD‐1 antibody, is known to promote the prol...

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Autores principales: MaruYama, Takashi, Kobayashi, Shuhei, Shibata, Hiroyuki, Chen, WanJun, Owada, Yuji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8645716/
https://www.ncbi.nlm.nih.gov/pubmed/34529884
http://dx.doi.org/10.1111/cas.15136
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author MaruYama, Takashi
Kobayashi, Shuhei
Shibata, Hiroyuki
Chen, WanJun
Owada, Yuji
author_facet MaruYama, Takashi
Kobayashi, Shuhei
Shibata, Hiroyuki
Chen, WanJun
Owada, Yuji
author_sort MaruYama, Takashi
collection PubMed
description Regulatory T cells (Tregs) in the tumor microenvironment regulate tumor immunity. Programmed cell death protein 1 (PD‐1) is known to be expressed on Tregs and plays crucial roles in suppressing tumor immunity. However, the immune checkpoint inhibitor, anti‐PD‐1 antibody, is known to promote the proliferation of the Treg population in tumor‐infiltrating lymphocytes, thereby restricting the efficacy of cancer immunotherapy. In this study, we focused on the curcumin analog GO‐Y030, an antitumor chemical. GO‐Y030 inhibited the immune‐suppressive ability of Tregs via metabolic changes in vitro, even in the presence of immune checkpoint inhibitors. Mechanistically, GO‐Y030 inhibited the mTOR‐S6 axis in Tregs, which plays a pivotal role in their immune‐suppressive ability. GO‐Y030 also controlled the metabolism in cultured CD4(+) T cells in the presence of TGF‐β + IL‐6; however, it did not prevent Th17 differentiation. Notably, GO‐Y030 significantly inhibited IL‐10 production from Th17 cells. In the tumor microenvironment, L‐lactate produced by tumors is known to support the suppressive ability of Tregs, and GO‐Y030 treatment inhibited L‐lactate production via metabolic changes. In addition, experiments in the B16‐F10 melanoma mouse model revealed that GO‐Y030 helped inhibit the anti‐PD‐1 immune checkpoint and reduce the Treg population in tumor‐infiltrating lymphocytes. Thus, GO‐Y030 controls the metabolism of both Tregs and tumors and could serve as a booster for anti‐immune checkpoint inhibitors.
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spelling pubmed-86457162021-12-17 Curcumin analog GO‐Y030 boosts the efficacy of anti‐PD‐1 cancer immunotherapy MaruYama, Takashi Kobayashi, Shuhei Shibata, Hiroyuki Chen, WanJun Owada, Yuji Cancer Sci Original Articles Regulatory T cells (Tregs) in the tumor microenvironment regulate tumor immunity. Programmed cell death protein 1 (PD‐1) is known to be expressed on Tregs and plays crucial roles in suppressing tumor immunity. However, the immune checkpoint inhibitor, anti‐PD‐1 antibody, is known to promote the proliferation of the Treg population in tumor‐infiltrating lymphocytes, thereby restricting the efficacy of cancer immunotherapy. In this study, we focused on the curcumin analog GO‐Y030, an antitumor chemical. GO‐Y030 inhibited the immune‐suppressive ability of Tregs via metabolic changes in vitro, even in the presence of immune checkpoint inhibitors. Mechanistically, GO‐Y030 inhibited the mTOR‐S6 axis in Tregs, which plays a pivotal role in their immune‐suppressive ability. GO‐Y030 also controlled the metabolism in cultured CD4(+) T cells in the presence of TGF‐β + IL‐6; however, it did not prevent Th17 differentiation. Notably, GO‐Y030 significantly inhibited IL‐10 production from Th17 cells. In the tumor microenvironment, L‐lactate produced by tumors is known to support the suppressive ability of Tregs, and GO‐Y030 treatment inhibited L‐lactate production via metabolic changes. In addition, experiments in the B16‐F10 melanoma mouse model revealed that GO‐Y030 helped inhibit the anti‐PD‐1 immune checkpoint and reduce the Treg population in tumor‐infiltrating lymphocytes. Thus, GO‐Y030 controls the metabolism of both Tregs and tumors and could serve as a booster for anti‐immune checkpoint inhibitors. John Wiley and Sons Inc. 2021-10-19 2021-12 /pmc/articles/PMC8645716/ /pubmed/34529884 http://dx.doi.org/10.1111/cas.15136 Text en © 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
MaruYama, Takashi
Kobayashi, Shuhei
Shibata, Hiroyuki
Chen, WanJun
Owada, Yuji
Curcumin analog GO‐Y030 boosts the efficacy of anti‐PD‐1 cancer immunotherapy
title Curcumin analog GO‐Y030 boosts the efficacy of anti‐PD‐1 cancer immunotherapy
title_full Curcumin analog GO‐Y030 boosts the efficacy of anti‐PD‐1 cancer immunotherapy
title_fullStr Curcumin analog GO‐Y030 boosts the efficacy of anti‐PD‐1 cancer immunotherapy
title_full_unstemmed Curcumin analog GO‐Y030 boosts the efficacy of anti‐PD‐1 cancer immunotherapy
title_short Curcumin analog GO‐Y030 boosts the efficacy of anti‐PD‐1 cancer immunotherapy
title_sort curcumin analog go‐y030 boosts the efficacy of anti‐pd‐1 cancer immunotherapy
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8645716/
https://www.ncbi.nlm.nih.gov/pubmed/34529884
http://dx.doi.org/10.1111/cas.15136
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