Tumor resident regulatory T cells.

The immune system mediates powerful effector mechanisms to protect against a diversity of pathogens and equally as important regulatory functions, to limit collateral damage of inflammation, prevent misguided immune responses to "self", and promote tissue repair. Inadequate regulatory control can lead to a variety of inflammatory disorders including autoimmunity, metabolic syndrome, allergies, and progression of malignancies. Cancers evolve complex mechanisms to thwart immune eradication including coopting normal host regulatory processes. This is most evident in the analysis of tumor infiltrating lymphocytes (TILs), where a preponderance of immunosuppressive immune cells, such as regulatory T (Treg) cells are found. Treg cells express the X-chromosome linked transcription factor Foxp3 and play a crucial role in maintaining immune homeostasis by suppressing inflammatory responses in diverse biological settings. Treg cells in the tumor microenvironment promote tumor development and progression by dampening anti-tumor immune responses, directly supporting the survival of transformed cells through elaboration of growth factors, and interacting with accessory cells in tumors such as fibroblasts and endothelial cells. Current insights into the phenotype and function of tumor associated Treg cells have opened up opportunities for their selective targeting in cancer with the goal of alleviating their suppression of anti-tumor immune responses while maintaining overall immune homeostasis. Here, we review Treg cell biology in the context of the tumor microenvironment (TME), and the important role they play in cancer immunotherapy.