PMID- 34503167
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210913
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 13
IP  - 17
DP  - 2021 Aug 28
TI  - Paliperidone Inhibits Glioblastoma Growth in Mouse Brain Tumor Model and Reduces 
      PD-L1 Expression.
LID - 10.3390/cancers13174357 [doi]
LID - 4357
AB  - 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.
FAU - Liu, Yu-Shu
AU  - Liu YS
AD  - Department of Pharmacology, School of Medicine, China Medical University, 
      Taichung 404, Taiwan.
FAU - Huang, Bor-Ren
AU  - Huang BR
AD  - Department of Neurosurgery, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical 
      Foundation, Taichung 404, Taiwan.
AD  - School of Medicine, Tzu Chi University, Taichung 404, Taiwan.
FAU - Lin, Ching-Ju
AU  - Lin CJ
AD  - Department of Physiology, School of Medicine, China Medical University, Taichung 
      404, Taiwan.
FAU - Shen, Ching-Kai
AU  - Shen CK
AD  - Graduate Institute of Biomedical Sciences, China Medical University, Taichung 
      404, Taiwan.
FAU - Lai, Sheng-Wei
AU  - Lai SW
AD  - Department of Pharmacology, School of Medicine, China Medical University, 
      Taichung 404, Taiwan.
FAU - Chen, Chao-Wei
AU  - Chen CW
AUID- ORCID: 0000-0002-9084-6741
AD  - Institute of New Drug Development, China Medical University, Taichung 404, 
      Taiwan.
FAU - Lin, Hui-Jung
AU  - Lin HJ
AD  - Department of Pharmacology, School of Medicine, China Medical University, 
      Taichung 404, Taiwan.
FAU - Lin, Chia-Huei
AU  - Lin CH
AD  - Department of Pharmacy, China Medical University, Taichung 404, Taiwan.
FAU - Hsieh, Yun-Chen
AU  - Hsieh YC
AD  - Department of Pharmacy, China Medical University, Taichung 404, Taiwan.
FAU - Lu, Dah-Yuu
AU  - Lu DY
AUID- ORCID: 0000-0002-4463-5919
AD  - Department of Pharmacology, School of Medicine, China Medical University, 
      Taichung 404, Taiwan.
AD  - Department of Photonics and Communication Engineering, Asia University, Taichung 
      404, Taiwan.
LA  - eng
GR  - CMU107-S-48/China Medical University, Taiwan/
PT  - Journal Article
DEP - 20210828
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC8430966
OTO - NOTNLM
OT  - DRD2
OT  - PD-L1
OT  - glioblastoma
OT  - paliperidone
OT  - tumor-associated macrophage
COIS- The authors declare no conflict of interest.
EDAT- 2021/09/11 06:00
MHDA- 2021/09/11 06:01
PMCR- 2021/08/28
CRDT- 2021/09/10 01:11
PHST- 2021/08/06 00:00 [received]
PHST- 2021/08/24 00:00 [accepted]
PHST- 2021/09/10 01:11 [entrez]
PHST- 2021/09/11 06:00 [pubmed]
PHST- 2021/09/11 06:01 [medline]
PHST- 2021/08/28 00:00 [pmc-release]
AID - cancers13174357 [pii]
AID - cancers-13-04357 [pii]
AID - 10.3390/cancers13174357 [doi]
PST - epublish
SO  - Cancers (Basel). 2021 Aug 28;13(17):4357. doi: 10.3390/cancers13174357.