Journal
SCIENCE ADVANCES
Volume 1, Issue 10, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.1500845
Keywords
-
Categories
Funding
- NIH [CA096651, CA103320, CA112431]
- Lovick P. and Elizabeth T. Corn Foundation [R01 HL11879, CA72669, R01 AI077610, R01 AI083005, AI103347]
- Ministry of Education, Culture, Sports, Science, and Technology, Japan [26290059]
- Grants-in-Aid for Scientific Research [26290059] Funding Source: KAKEN
Ask authors/readers for more resources
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 (T-reg) activation dependent on the PTEN (phosphatase and tensin homolog) lipid phosphatase. PTEN acted to stabilize T-regs in tumors, preventing them from reprogramming into inflammatory effector cells. In mice with a T-reg-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 T-regs, 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 T-regs is disrupted.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available