Strong-arming immune regulation: suppressing regulatory T-cell function to treat cancers

In recent years there has been an accelerated understanding of immune regulatory mechanisms. Much of this immune regulation is linked to a collection of specialized regulatory cells of the T-cell lineage (Tregs). This collection consists of Tregs that are either thymically derived or peripherally induced. Tregs are important for controlling potentially autoreactive immune effectors and immune responses to foreign organisms and molecules. Their importance in maintaining immune homeostasis and the overall health of an organism cannot be overstated. However, there is a dark side, and Tregs may also be involved in the pathogenesis of malignancies. Evidence shows that tumors induce or recruit Tregs to block antitumor effectors. Thus, there are efforts underway to identify approaches that specifically inhibit the function of intratumoral Tregs, which could lead to increased immunity to tumors without off-target immune-related pathologies (i.e., autoimmune disease). In this review, the biology of Tregs is discussed along with their involvement in malignancies and emerging strategies to block their function.