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HERO ID
7349395
Reference Type
Journal Article
Title
Systematically understanding the immunity leading to CRPC progression
Author(s)
Ji, Z; Zhao, W; Lin, HK; Zhou, X
Year
2019
Is Peer Reviewed?
1
Journal
PLoS Computational Biology
ISSN:
1553-734X
EISSN:
1553-7358
Volume
15
Issue
9
Page Numbers
e1007344
Language
English
PMID
31504033
DOI
10.1371/journal.pcbi.1007344
Web of Science Id
WOS:000489741800037
Abstract
Prostate cancer (PCa) is the most commonly diagnosed malignancy and the second leading cause of cancer-related death in American men. Androgen deprivation therapy (ADT) has become a standard treatment strategy for advanced PCa. Although a majority of patients initially respond to ADT well, most of them will eventually develop castration-resistant PCa (CRPC). Previous studies suggest that ADT-induced changes in the immune microenvironment (mE) in PCa might be responsible for the failures of various therapies. However, the role of the immune system in CRPC development remains unclear. To systematically understand the immunity leading to CRPC progression and predict the optimal treatment strategy in silico, we developed a 3D Hybrid Multi-scale Model (HMSM), consisting of an ODE system and an agent-based model (ABM), to manipulate the tumor growth in a defined immune system. Based on our analysis, we revealed that the key factors (e.g. WNT5A, TRAIL, CSF1, etc.) mediated the activation of PC-Treg and PC-TAM interaction pathways, which induced the immunosuppression during CRPC progression. Our HMSM model also provided an optimal therapeutic strategy for improving the outcomes of PCa treatment.
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