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

• DOI: 10.1126/sciadv.1500845
• Publication Date: 2015-11-07T04:09:27Z
• Authors: Madhav D. Sharma; Rahul Shinde; Tracy L. McGaha; Lei Huang; Rikke B. Holmgaard; Jedd D. Wolchok; Mario R. Mautino; Esteban Celis; Arlene H. Sharpe; Loise M. Francisco; Jonathan D. Powell; Hideo Yagita; Andrew L. Mellor; Bruce R. Blazar; David H. Munn
• Keywords: 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

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.