The PTEN pathway in Tregs is a critical driver of the suppressive tumor microenvironment

DSpace/Manakin Repository

The PTEN pathway in Tregs is a critical driver of the suppressive tumor microenvironment

Citable link to this page

 

 
Title: The PTEN pathway in Tregs is a critical driver of the suppressive tumor microenvironment
Author: Sharma, Madhav D.; Shinde, Rahul; McGaha, Tracy L.; Huang, Lei; Holmgaard, Rikke B.; Wolchok, Jedd D.; Mautino, Mario R.; Celis, Esteban; Sharpe, Arlene H.; Francisco, Loise M.; Powell, Jonathan D.; Yagita, Hideo; Mellor, Andrew L.; Blazar, Bruce R.; Munn, David H.

Note: Order does not necessarily reflect citation order of authors.

Citation: Sharma, M. D., R. Shinde, T. L. McGaha, L. Huang, R. B. Holmgaard, J. D. Wolchok, M. R. Mautino, et al. 2015. “The PTEN pathway in Tregs is a critical driver of the suppressive tumor microenvironment.” Science Advances 1 (10): e1500845. doi:10.1126/sciadv.1500845. http://dx.doi.org/10.1126/sciadv.1500845.
Full Text & Related Files:
Abstract: The tumor microenvironment is profoundly immunosuppressive. We show that multiple tumor types create intratumoral immune suppression driven by a specialized form of regulatory T cell (Treg) activation dependent on the PTEN (phosphatase and tensin homolog) lipid phosphatase. PTEN acted to stabilize Tregs in tumors, preventing them from reprogramming into inflammatory effector cells. In mice with a Treg-specific deletion of PTEN, tumors grew slowly, were inflamed, and could not create an immunosuppressive tumor microenvironment. In normal mice, exposure to apoptotic tumor cells rapidly elicited PTEN-expressing Tregs, and PTEN-deficient mice were unable to maintain tolerance to apoptotic cells. In wild-type mice with large established tumors, pharmacologic inhibition of PTEN after chemotherapy or immunotherapy profoundly reconfigured the tumor microenvironment, changing it from a suppressive to an inflammatory milieu, and tumors underwent rapid regression. Thus, the immunosuppressive milieu in tumors must be actively maintained, and tumors become susceptible to immune attack if the PTEN pathway in Tregs is disrupted.
Published Version: doi:10.1126/sciadv.1500845
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4640592/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:23845142
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters