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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-11-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.759172/full |
| _version_ | 1818920604219211776 |
|---|---|
| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-20T01:24:23Z |
| format | Article |
| id | doaj.art-259294ad69584921bf0709d67c689e9f |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-20T01:24:23Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-259294ad69584921bf0709d67c689e9f2022-12-21T19:58:16ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-11-011210.3389/fphar.2021.759172759172Hydroxytyrosol Inhibits MDSCs and Promotes M1 Macrophages in Mice With Orthotopic Pancreatic TumorBotao Wang0Botao Wang1Lei Yang2Tianyu Liu3Tianyu Liu4Jing Xun5Yuzhen Zhuo6Lanqiu Zhang7Qi Zhang8Qi Zhang9Ximo Wang10Ximo Wang11Ximo Wang12Graduate School, Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Institute of Acute Abdominal Diseases, Tianjin Nankai Hospital, Tianjin, ChinaTianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Institute of Acute Abdominal Diseases, Tianjin Nankai Hospital, Tianjin, ChinaGraduate School, Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Institute of Acute Abdominal Diseases, Tianjin Nankai Hospital, Tianjin, ChinaTianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Institute of Acute Abdominal Diseases, Tianjin Nankai Hospital, Tianjin, ChinaTianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Institute of Acute Abdominal Diseases, Tianjin Nankai Hospital, Tianjin, ChinaTianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Institute of Acute Abdominal Diseases, Tianjin Nankai Hospital, Tianjin, ChinaState Key Laboratory of Medicinal Chemical Biology, NanKai University, Tianjin, ChinaTianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Institute of Integrative Medicine for Acute Abdominal Diseases, Integrated Chinese and Western Medicine Hospital, Tianjin University, Tianjin, ChinaGraduate School, Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Institute of Integrative Medicine for Acute Abdominal Diseases, Integrated Chinese and Western Medicine Hospital, Tianjin University, Tianjin, ChinaThe Clinical Research Center of Tianjin for Treating Acute Abdominal Diseases with Integrated Medicine, Tianjin, ChinaThe 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.https://www.frontiersin.org/articles/10.3389/fphar.2021.759172/fullhydroxytyrosolpancreatic cancerMDSCsM1 macrophagesstat3 |
| spellingShingle | 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 Frontiers in Pharmacology hydroxytyrosol pancreatic cancer MDSCs M1 macrophages stat3 |
| title | 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_short | 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 |
| topic | hydroxytyrosol pancreatic cancer MDSCs M1 macrophages stat3 |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.759172/full |
| work_keys_str_mv | AT botaowang hydroxytyrosolinhibitsmdscsandpromotesm1macrophagesinmicewithorthotopicpancreatictumor AT botaowang hydroxytyrosolinhibitsmdscsandpromotesm1macrophagesinmicewithorthotopicpancreatictumor AT leiyang hydroxytyrosolinhibitsmdscsandpromotesm1macrophagesinmicewithorthotopicpancreatictumor AT tianyuliu hydroxytyrosolinhibitsmdscsandpromotesm1macrophagesinmicewithorthotopicpancreatictumor AT tianyuliu hydroxytyrosolinhibitsmdscsandpromotesm1macrophagesinmicewithorthotopicpancreatictumor AT jingxun hydroxytyrosolinhibitsmdscsandpromotesm1macrophagesinmicewithorthotopicpancreatictumor AT yuzhenzhuo hydroxytyrosolinhibitsmdscsandpromotesm1macrophagesinmicewithorthotopicpancreatictumor AT lanqiuzhang hydroxytyrosolinhibitsmdscsandpromotesm1macrophagesinmicewithorthotopicpancreatictumor AT qizhang hydroxytyrosolinhibitsmdscsandpromotesm1macrophagesinmicewithorthotopicpancreatictumor AT qizhang hydroxytyrosolinhibitsmdscsandpromotesm1macrophagesinmicewithorthotopicpancreatictumor AT ximowang hydroxytyrosolinhibitsmdscsandpromotesm1macrophagesinmicewithorthotopicpancreatictumor AT ximowang hydroxytyrosolinhibitsmdscsandpromotesm1macrophagesinmicewithorthotopicpancreatictumor AT ximowang hydroxytyrosolinhibitsmdscsandpromotesm1macrophagesinmicewithorthotopicpancreatictumor |