UM  > 中華醫藥研究院
Blockade of TNFR2 signaling enhances the immunotherapeutic effect of CpG ODN in a mouse model of colon cancer
Nie, Yingjie1,2; He, Jiang3; Shirota, Hidekazu1; Trivett, Anna L.1; Yang, De1; Klinman, Dennis M.1; Oppenheim, Joost J.1; Chen, Xin1,3
2018-01-02
Source PublicationSCIENCE SIGNALING
ISSN1945-0877
Volume11Issue:511
Abstract

Through the tumor necrosis factor (TNF) receptor type II (TNFR2), TNF preferentially activates, expands, and promotes the phenotypic stability of CD4(+)Foxp3(+) regulatory T (T-reg) cells. Those T-reg cells that have a high abundance of TNFR2 have the maximal immunosuppressive capacity. We investigated whether targeting TNFR2 could effectively suppress the activity of T-reg cells and consequently enhance the efficacy of cancer immunotherapy. We found that, relative to a suboptimal dose of the immunostimulatory Toll-like receptor 9 ligand CpG oligodeoxynucleotide (ODN), the combination of the suboptimal dose of CpG ODN with the TNFR2-blocking antibody M861 more markedly inhibited the growth of subcutaneously grafted mouse CT26 colon tumor cells. This resulted in markedly fewer TNFR2(+) T-reg cells and more interferon-gamma-positive (IFN-gamma(+)) CD8(+) cytotoxic T lymphocytes infiltrating the tumor and improved long-term tumor-free survival in the mouse cohort. Tumor-free mice were resistant to rechallenge by the same but not unrelated (4T1 breast cancer) cells. Treatment with the combination of TNFR2-blocking antibody and a CD25-targeted antibody also resulted in enhanced inhibition of tumor growth in a syngeneic 4T1 mouse model of breast cancer. Thus, the combination of a TNFR2 inhibitor and an immunotherapeutic stimulant may represent a more effective treatment strategy for various cancers.

DOI10.1126/scisignal.aan0790
URLView the original
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology ; Cell Biology
WOS SubjectBiochemistry & Molecular Biology ; Cell Biology
WOS IDWOS:000419220100003
PublisherAMER ASSOC ADVANCEMENT SCIENCE
The Source to ArticleWOS
Fulltext Access
Citation statistics
Cited Times [WOS]:13   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Cancer Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
2.Department of Research, Guizhou Provincial People’s Hospital, Guiyang, Guizhou 550002, China.
3.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR 999078, China.
Recommended Citation
GB/T 7714
Nie, Yingjie,He, Jiang,Shirota, Hidekazu,et al. Blockade of TNFR2 signaling enhances the immunotherapeutic effect of CpG ODN in a mouse model of colon cancer[J]. SCIENCE SIGNALING,2018,11(511).
APA Nie, Yingjie.,He, Jiang.,Shirota, Hidekazu.,Trivett, Anna L..,Yang, De.,...&Chen, Xin.(2018).Blockade of TNFR2 signaling enhances the immunotherapeutic effect of CpG ODN in a mouse model of colon cancer.SCIENCE SIGNALING,11(511).
MLA Nie, Yingjie,et al."Blockade of TNFR2 signaling enhances the immunotherapeutic effect of CpG ODN in a mouse model of colon cancer".SCIENCE SIGNALING 11.511(2018).
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Nie, Yingjie]'s Articles
[He, Jiang]'s Articles
[Shirota, Hidekazu]'s Articles
Baidu academic
Similar articles in Baidu academic
[Nie, Yingjie]'s Articles
[He, Jiang]'s Articles
[Shirota, Hidekazu]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Nie, Yingjie]'s Articles
[He, Jiang]'s Articles
[Shirota, Hidekazu]'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.