Regulatory T Cells in Cancer

The immune system has evolved complex effector mechanisms to protect the host against a diversity of pathogenic organisms and regulatory adaptations that can curtail pathological sequelae of inflammatory events, prevent autoimmunity, and assist in tissue repair. Cancers, by virtue of their local manifestations of tissue dysfunction and destruction, inflammation, and genomic instability, can evoke these protective mechanisms, which support the progression of tumors and prevent their immune eradication. Central to these processes is a subset of CD4+ T cells, known as regulatory T (Treg) cells, that express the X chromosome–linked transcription factor FOXP3. In addition to their critical role in controlling autoimmunity and suppressing inflammatory responses in diverse biological settings, Treg cells are ubiquitously present in the tumor microenvironment where they promote tumor development and progression by dampening antitumor immune responses. Furthermore, Treg cells can directly support the survival of transformed cells through the elaboration of growth factors and interacting with accessory cells in tumors such as fibroblasts and endothelial cells. Current insights into the biology of tumor-associated Treg cells have opened up opportunities for their selective targeting in cancer, with the goal of alleviating their suppression of antitumor immune responses while maintaining overall immune homeostasis.