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

PTEN indoleamine 2,3-dioxygenase SciAdv r-articles 610 Tregs Regulatory T cells Cancer Immunotherapy 3. Good health 03 medical and health sciences 0302 clinical medicine tumor microenvironment tumor immunology 14. Life underwater Research Articles
DOI: 10.1126/sciadv.1500845 Publication Date: 2015-11-07T04:09:27Z
ABSTRACT
The tumor microenvironment is profoundly immunosuppressive. We show that multiple 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. acted to stabilize Tregs in tumors, preventing them from reprogramming into inflammatory effector cells. In mice with Treg-specific deletion PTEN, tumors grew slowly, were inflamed, could not an immunosuppressive microenvironment. normal mice, exposure apoptotic cells rapidly elicited PTEN-expressing Tregs, PTEN-deficient unable maintain tolerance wild-type large established pharmacologic inhibition after chemotherapy or immunotherapy reconfigured microenvironment, changing it suppressive milieu, underwent rapid regression. Thus, milieu must be actively maintained, become susceptible attack if pathway disrupted.
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