Systematically understanding the immunity leading to CRPC progression

被引:27
|
作者
Ji, Zhiwei [1 ]
Zhao, Weiling [1 ]
Lin, Hui-Kuan [2 ]
Zhou, Xiaobo [1 ]
机构
[1] Univ Texas Hlth Sci Ctr Houston, Sch Biomed Informat, Houston, TX 77030 USA
[2] Wake Forest Univ, Wake Forest Baptist Med Ctr, Dept Canc Biol, Winston Salem, NC 27101 USA
基金
美国国家卫生研究院;
关键词
REGULATORY T-CELLS; TUMOR-ASSOCIATED MACROPHAGES; RESISTANT PROSTATE-CANCER; ANDROGEN RECEPTOR; DENDRITIC CELLS; UP-REGULATION; LIGAND TRAIL; RNA-SEQ; CASTRATION; EXPRESSION;
D O I
10.1371/journal.pcbi.1007344
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页数:29
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