Home sweet home: the tumor microenvironment as a haven for regulatory T cells

• ¹Nuffield Department of Medicine, The Jenner Institute (ORCRB), University of Oxford, Oxford, UK
• ²Infection and Immunity, School of Medicine, Henry Wellcome Building, Cardiff University, Cardiff, UK

CD4⁺Foxp3⁺ regulatory T cells (T_regs) have a fundamental role in maintaining immune balance by preventing autoreactivity and immune-mediated pathology. However this role of T_regs extends to suppression of anti-tumor immune responses and remains a major obstacle in the development of anti-cancer vaccines and immunotherapies. This feature of T_reg activity is exacerbated by the discovery that T_reg frequencies are not only elevated in the blood of cancer patients, but are also significantly enriched within tumors in comparison to other sites. These observations have sparked off the quest to understand the processes through which T_regs become elevated in cancer-bearing hosts and to identify the specific mechanisms leading to their accumulation within the tumor microenvironment. This manuscript reviews the evidence for specific mechanisms of intra-tumoral T_reg enrichment and will discuss how this information may be utilized for the purpose of manipulating the balance of tumor-infiltrating T cells in favor of anti-tumor effector cells.