CD4+CD25+Foxp3+ regulatory T cells (Tregs) are increased in the peripheral circulation of patients suffering from many different types of cancers and can prevent protective antitumor immunity from optimal functioning. Properties of Tregs in the solid tumor mass and its draining lymph nodes may differ compared to Tregs in peripheral circulation, making studies of tumor microenvironmental Tregs the focus of more recent work. These tumor-associated Tregs are heterogeneous with respect to mechanisms of their origin and in their mechanisms for regulating and impeding successful antitumor immunity. Although many studies now report that tumor Treg content inversely correlates with survival or therapeutic response, there are conflicting data, including reports that Tregs are beneficial in some types of cancers. Strategies to manage Treg-mediated immune dysfunction for therapeutic purposes include depleting Tregs, blocking their regulatory functions or differentiation, altering their trafficking, diverting them into a different T cell differentiation pathway, or raising the effector cell threshold to Treg-mediated regulation. Several clinical trials have now been conducted demonstrating the feasibility and relative safety of managing Tregs in human cancer. This chapter surveys current understandings of Tregs in malignancies, including their origins, mechanisms of action, interactions with other immune cells and strategies to manage them therapeutically. Other regulatory cells in cancer will be addressed in brief.
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