Hydroxytyrosol Inhibits MDSCs and Promotes M1 Macrophages in Mice With Orthotopic Pancreatic Tumor

The poor immunotherapy of pancreatic cancer is mainly due to its complex immunosuppressive microenvironment. The Mediterranean diet contributes to low cancer incidence. Hydroxytyrosol (HT) derived from olive oil has multiple health-promoting effects, but its therapeutic effect on pancreatic cancer r...

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Autores principales:	Botao Wang, Lei Yang, Tianyu Liu, Jing Xun, Yuzhen Zhuo, Lanqiu Zhang, Qi Zhang, Ximo Wang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	hydroxytyrosol pancreatic cancer MDSCs M1 macrophages stat3 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/259294ad69584921bf0709d67c689e9f
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spelling	oai:doaj.org-article:259294ad69584921bf0709d67c689e9f2021-11-11T10:15:31ZHydroxytyrosol Inhibits MDSCs and Promotes M1 Macrophages in Mice With Orthotopic Pancreatic Tumor1663-981210.3389/fphar.2021.759172https://doaj.org/article/259294ad69584921bf0709d67c689e9f2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.759172/fullhttps://doaj.org/toc/1663-9812The poor immunotherapy of pancreatic cancer is mainly due to its complex immunosuppressive microenvironment. The Mediterranean diet contributes to low cancer incidence. Hydroxytyrosol (HT) derived from olive oil has multiple health-promoting effects, but its therapeutic effect on pancreatic cancer remains controversial. Here, we evaluated the inhibitory effect of HT on mouse pancreatic cancer, and the effect of HT on the immune microenvironment. We found that HT can inhibit the proliferation of Panc 02 cells through signal transducer and activator of transcription (STAT) 3/Cyclin D1 signaling pathway. In the tumor-bearing mice treated with HT, the orthotopic pancreatic tumors were suppressed, accompanied by a decrease in the proportion of myeloid-derived suppressor cells (MDSCs) and an increase in the proportion of M1 macrophages. In addition, we found that HT inhibited the expression of immunosuppressive molecules in bone marrow (BM)-derived MDSCs, as well as down-regulated CCAAT/enhancer-binding protein beta (C/EBPβ) and phosphorylation of STAT3. Moreover, HT enhanced the anti-tumor effect of anti-CD47 antibody in vivo. HT combined with plumbagin (PLB) induced more Panc 02 cells death than HT or PLB alone. This combination therapy not only inhibited the accumulation of MDSCs, but also promoted the infiltration of CD4+ and CD8+ T cells in the tumors. In summary, HT is a potential immunomodulatory drug for the treatment of pancreatic cancer.Botao WangBotao WangLei YangTianyu LiuTianyu LiuJing XunYuzhen ZhuoLanqiu ZhangQi ZhangQi ZhangXimo WangXimo WangXimo WangFrontiers Media S.A.articlehydroxytyrosolpancreatic cancerMDSCsM1 macrophagesstat3Therapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hydroxytyrosol pancreatic cancer MDSCs M1 macrophages stat3 Therapeutics. Pharmacology RM1-950
spellingShingle	hydroxytyrosol pancreatic cancer MDSCs M1 macrophages stat3 Therapeutics. Pharmacology RM1-950 Botao Wang Botao Wang Lei Yang Tianyu Liu Tianyu Liu Jing Xun Yuzhen Zhuo Lanqiu Zhang Qi Zhang Qi Zhang Ximo Wang Ximo Wang Ximo Wang Hydroxytyrosol Inhibits MDSCs and Promotes M1 Macrophages in Mice With Orthotopic Pancreatic Tumor
description	The poor immunotherapy of pancreatic cancer is mainly due to its complex immunosuppressive microenvironment. The Mediterranean diet contributes to low cancer incidence. Hydroxytyrosol (HT) derived from olive oil has multiple health-promoting effects, but its therapeutic effect on pancreatic cancer remains controversial. Here, we evaluated the inhibitory effect of HT on mouse pancreatic cancer, and the effect of HT on the immune microenvironment. We found that HT can inhibit the proliferation of Panc 02 cells through signal transducer and activator of transcription (STAT) 3/Cyclin D1 signaling pathway. In the tumor-bearing mice treated with HT, the orthotopic pancreatic tumors were suppressed, accompanied by a decrease in the proportion of myeloid-derived suppressor cells (MDSCs) and an increase in the proportion of M1 macrophages. In addition, we found that HT inhibited the expression of immunosuppressive molecules in bone marrow (BM)-derived MDSCs, as well as down-regulated CCAAT/enhancer-binding protein beta (C/EBPβ) and phosphorylation of STAT3. Moreover, HT enhanced the anti-tumor effect of anti-CD47 antibody in vivo. HT combined with plumbagin (PLB) induced more Panc 02 cells death than HT or PLB alone. This combination therapy not only inhibited the accumulation of MDSCs, but also promoted the infiltration of CD4+ and CD8+ T cells in the tumors. In summary, HT is a potential immunomodulatory drug for the treatment of pancreatic cancer.
format	article
author	Botao Wang Botao Wang Lei Yang Tianyu Liu Tianyu Liu Jing Xun Yuzhen Zhuo Lanqiu Zhang Qi Zhang Qi Zhang Ximo Wang Ximo Wang Ximo Wang
author_facet	Botao Wang Botao Wang Lei Yang Tianyu Liu Tianyu Liu Jing Xun Yuzhen Zhuo Lanqiu Zhang Qi Zhang Qi Zhang Ximo Wang Ximo Wang Ximo Wang
author_sort	Botao Wang
title	Hydroxytyrosol Inhibits MDSCs and Promotes M1 Macrophages in Mice With Orthotopic Pancreatic Tumor
title_short	Hydroxytyrosol Inhibits MDSCs and Promotes M1 Macrophages in Mice With Orthotopic Pancreatic Tumor
title_full	Hydroxytyrosol Inhibits MDSCs and Promotes M1 Macrophages in Mice With Orthotopic Pancreatic Tumor
title_fullStr	Hydroxytyrosol Inhibits MDSCs and Promotes M1 Macrophages in Mice With Orthotopic Pancreatic Tumor
title_full_unstemmed	Hydroxytyrosol Inhibits MDSCs and Promotes M1 Macrophages in Mice With Orthotopic Pancreatic Tumor
title_sort	hydroxytyrosol inhibits mdscs and promotes m1 macrophages in mice with orthotopic pancreatic tumor
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/259294ad69584921bf0709d67c689e9f
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Hydroxytyrosol Inhibits MDSCs and Promotes M1 Macrophages in Mice With Orthotopic Pancreatic Tumor

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