Paliperidone Inhibits Glioblastoma Growth in Mouse Brain Tumor Model and Reduces PD-L1 Expression
A previous study from our group reported that monocyte adhesion to glioblastoma (GBM) promoted tumor growth and invasion activity and increased tumor-associated macrophages (TAMs) proliferation and inflammatory mediator secretion as well. The present study showed that prescribed psychotropic medicin...
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MDPI AG
2021-08-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/17/4357 |
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| author | Yu-Shu Liu Bor-Ren Huang Ching-Ju Lin Ching-Kai Shen Sheng-Wei Lai Chao-Wei Chen Hui-Jung Lin Chia-Huei Lin Yun-Chen Hsieh Dah-Yuu Lu |
| author_facet | Yu-Shu Liu Bor-Ren Huang Ching-Ju Lin Ching-Kai Shen Sheng-Wei Lai Chao-Wei Chen Hui-Jung Lin Chia-Huei Lin Yun-Chen Hsieh Dah-Yuu Lu |
| author_sort | Yu-Shu Liu |
| collection | DOAJ |
| description | A previous study from our group reported that monocyte adhesion to glioblastoma (GBM) promoted tumor growth and invasion activity and increased tumor-associated macrophages (TAMs) proliferation and inflammatory mediator secretion as well. The present study showed that prescribed psychotropic medicine paliperidone reduced GBM growth and immune checkpoint protein programmed death ligand (PD-L)1 expression and increased survival in an intracranial xenograft mouse model. An analysis of the database of patients with glioma showed that the levels of PD-L1 and dopamine receptor D (DRD)2 were higher in the GBM group than in the low grade astrocytoma and non-tumor groups. In addition, GFP expressing GBM (GBM-GFP) cells co-cultured with monocytes-differentiated macrophage enhanced PD-L1 expression in GBM cells. The enhancement of PD-L1 in GBM was antagonized by paliperidone and risperidone as well as DRD2 selective inhibitor L741426. The expression of CD206 (M2 phenotype marker) was observed to be markedly increased in bone marrow-derived macrophages (BMDMs) co-cultured with GBM. Importantly, treatment with paliperidone effectively decreased CD206 and also dramatically increased CD80 (M1 phenotype marker) in BMDMs. We have previously established a PD-L1 GBM-GFP cell line that stably expresses PD-L1. Experiments showed that the expressions of CD206 was increased and CD80 was mildly decreased in the BMDMs co-cultured with PD-L1 GBM-GFP cells. On the other hands, knockdown of DRD2 expression in GBM cells dramatically decreased the expression of CD206 but markedly increased CD80 expressions in BMDMs. The present study suggests that DRD2 may be involved in regulating the PD-L1 expression in GBM and the microenvironment of GBM. Our results provide a valuable therapeutic strategy and indicate that treatments combining DRD2 antagonist paliperidone with standard immunotherapy may be beneficial for GBM treatment. |
| first_indexed | 2024-03-10T08:14:35Z |
| format | Article |
| id | doaj.art-6841829829a64365b9df91f08df25054 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T08:14:35Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-6841829829a64365b9df91f08df250542023-11-22T10:26:11ZengMDPI AGCancers2072-66942021-08-011317435710.3390/cancers13174357Paliperidone Inhibits Glioblastoma Growth in Mouse Brain Tumor Model and Reduces PD-L1 ExpressionYu-Shu Liu0Bor-Ren Huang1Ching-Ju Lin2Ching-Kai Shen3Sheng-Wei Lai4Chao-Wei Chen5Hui-Jung Lin6Chia-Huei Lin7Yun-Chen Hsieh8Dah-Yuu Lu9Department of Pharmacology, School of Medicine, China Medical University, Taichung 404, TaiwanDepartment of Neurosurgery, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 404, TaiwanDepartment of Physiology, School of Medicine, China Medical University, Taichung 404, TaiwanGraduate Institute of Biomedical Sciences, China Medical University, Taichung 404, TaiwanDepartment of Pharmacology, School of Medicine, China Medical University, Taichung 404, TaiwanInstitute of New Drug Development, China Medical University, Taichung 404, TaiwanDepartment of Pharmacology, School of Medicine, China Medical University, Taichung 404, TaiwanDepartment of Pharmacy, China Medical University, Taichung 404, TaiwanDepartment of Pharmacy, China Medical University, Taichung 404, TaiwanDepartment of Pharmacology, School of Medicine, China Medical University, Taichung 404, TaiwanA previous study from our group reported that monocyte adhesion to glioblastoma (GBM) promoted tumor growth and invasion activity and increased tumor-associated macrophages (TAMs) proliferation and inflammatory mediator secretion as well. The present study showed that prescribed psychotropic medicine paliperidone reduced GBM growth and immune checkpoint protein programmed death ligand (PD-L)1 expression and increased survival in an intracranial xenograft mouse model. An analysis of the database of patients with glioma showed that the levels of PD-L1 and dopamine receptor D (DRD)2 were higher in the GBM group than in the low grade astrocytoma and non-tumor groups. In addition, GFP expressing GBM (GBM-GFP) cells co-cultured with monocytes-differentiated macrophage enhanced PD-L1 expression in GBM cells. The enhancement of PD-L1 in GBM was antagonized by paliperidone and risperidone as well as DRD2 selective inhibitor L741426. The expression of CD206 (M2 phenotype marker) was observed to be markedly increased in bone marrow-derived macrophages (BMDMs) co-cultured with GBM. Importantly, treatment with paliperidone effectively decreased CD206 and also dramatically increased CD80 (M1 phenotype marker) in BMDMs. We have previously established a PD-L1 GBM-GFP cell line that stably expresses PD-L1. Experiments showed that the expressions of CD206 was increased and CD80 was mildly decreased in the BMDMs co-cultured with PD-L1 GBM-GFP cells. On the other hands, knockdown of DRD2 expression in GBM cells dramatically decreased the expression of CD206 but markedly increased CD80 expressions in BMDMs. The present study suggests that DRD2 may be involved in regulating the PD-L1 expression in GBM and the microenvironment of GBM. Our results provide a valuable therapeutic strategy and indicate that treatments combining DRD2 antagonist paliperidone with standard immunotherapy may be beneficial for GBM treatment.https://www.mdpi.com/2072-6694/13/17/4357DRD2glioblastomaPD-L1tumor-associated macrophagepaliperidone |
| spellingShingle | Yu-Shu Liu Bor-Ren Huang Ching-Ju Lin Ching-Kai Shen Sheng-Wei Lai Chao-Wei Chen Hui-Jung Lin Chia-Huei Lin Yun-Chen Hsieh Dah-Yuu Lu Paliperidone Inhibits Glioblastoma Growth in Mouse Brain Tumor Model and Reduces PD-L1 Expression Cancers DRD2 glioblastoma PD-L1 tumor-associated macrophage paliperidone |
| title | Paliperidone Inhibits Glioblastoma Growth in Mouse Brain Tumor Model and Reduces PD-L1 Expression |
| title_full | Paliperidone Inhibits Glioblastoma Growth in Mouse Brain Tumor Model and Reduces PD-L1 Expression |
| title_fullStr | Paliperidone Inhibits Glioblastoma Growth in Mouse Brain Tumor Model and Reduces PD-L1 Expression |
| title_full_unstemmed | Paliperidone Inhibits Glioblastoma Growth in Mouse Brain Tumor Model and Reduces PD-L1 Expression |
| title_short | Paliperidone Inhibits Glioblastoma Growth in Mouse Brain Tumor Model and Reduces PD-L1 Expression |
| title_sort | paliperidone inhibits glioblastoma growth in mouse brain tumor model and reduces pd l1 expression |
| topic | DRD2 glioblastoma PD-L1 tumor-associated macrophage paliperidone |
| url | https://www.mdpi.com/2072-6694/13/17/4357 |
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