UM  > 中華醫藥研究院
A Jak2-selective inhibitor potently reverses the immune suppression by modulating the tumor microenvironment for cancer immunotherapy
He, Wei1; Zhu, Yi2; Mu, Ruoyu1; Xu, Jinzhi1; Zhang, Xiaoyi3; Wang, Chunming5; Li, Qiu5; Huang, Zhen1; Zhang, Junfeng1,4; Pan, Yi2; Han, Jianlin2; Dong, Lei1
2017-12
Source PublicationBIOCHEMICAL PHARMACOLOGY
ISSN0006-2952
Volume145Pages:132-146
Abstract

Small molecule therapeutics can be potent tools for cancer immunotherapy. They may be devised to target the tumor associated macrophages (TAMs) and regulatory T cells (Treg), which are major immunosuppressive cells in the tumor microenvironment. The infiltration and functionalization of these cells, which essentially promote tumor development, are mediated by the hyper-activation of the Jak-STAT3 signaling pathway. Here, we demonstrated that compound 9#, a novel inhibitor of Jak2, could suppress Jak2-STAT3 signaling in macrophages (peritoneal macrophages and THP-1 cells) and direct the macrophages toward the pro-inflammatory (M1-like) phenotype. When tested in ex vivo TAM culture and in vivo tumor models, compound 9# could reverse the phenotype of TAM from M2- to M1-type by promoting IL-12 expression. Further study suggested that compound 9# also inhibited the induction of Treg both in vitro and in vivo via blockage of Jak2 signaling. Finally, compound 9# potently increased the frequency and anti-tumor activity of CD4(+) and CD/8(+) T lymphocytes, leading to effective suppression of tumor growth. Taken together, our findings indicated that compound 9# could be a potential candidate of small molecule therapeutics for cancer immunotherapy. (C) 2017 Elsevier Inc. All rights reserved.

KeywordTumor Associated Macrophages Regulatory t Cells Jak2-stat3 Pathway Tumor Immunotherapy
DOI10.1016/j.bcp.2017.08.019
URLView the original
Indexed BySCI
Language英语
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000415784600014
PublisherPERGAMON-ELSEVIER SCIENCE LTD
The Source to ArticleWOS
Fulltext Access
Citation statistics
Cited Times [WOS]:4   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Co-First AuthorHe, Wei
Corresponding AuthorDong, Lei
Affiliation1.State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing 210093, China
2.School of Chemistry and Chemical Engineering, State Key laboratory of Coordination Chemistry, Nanjing University, Nanjing 210093, China
3.Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, GA 30322, USA
4.Jiangsu Provincial Laboratory for Nano-Technology, Nanjing University, Nanjing, China
5.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau
Recommended Citation
GB/T 7714
He, Wei,Zhu, Yi,Mu, Ruoyu,et al. A Jak2-selective inhibitor potently reverses the immune suppression by modulating the tumor microenvironment for cancer immunotherapy[J]. BIOCHEMICAL PHARMACOLOGY,2017,145:132-146.
APA He, Wei.,Zhu, Yi.,Mu, Ruoyu.,Xu, Jinzhi.,Zhang, Xiaoyi.,...&Dong, Lei.(2017).A Jak2-selective inhibitor potently reverses the immune suppression by modulating the tumor microenvironment for cancer immunotherapy.BIOCHEMICAL PHARMACOLOGY,145,132-146.
MLA He, Wei,et al."A Jak2-selective inhibitor potently reverses the immune suppression by modulating the tumor microenvironment for cancer immunotherapy".BIOCHEMICAL PHARMACOLOGY 145(2017):132-146.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[He, Wei]'s Articles
[Zhu, Yi]'s Articles
[Mu, Ruoyu]'s Articles
Baidu academic
Similar articles in Baidu academic
[He, Wei]'s Articles
[Zhu, Yi]'s Articles
[Mu, Ruoyu]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[He, Wei]'s Articles
[Zhu, Yi]'s Articles
[Mu, Ruoyu]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.