Regulatory T-cell heterogeneity and the cancer immune response

The frequency of circulating or tumour-infiltrating regulatory T cells (Tregs) has been associated with poor patient survival in many cancers including breast, melanoma and lung. It has been hypothesised that Tregs impact the anti-tumour function of effector T cells, resulting in worse outcomes for patients. However, high infiltrates of Tregs have been associated with a positive outcome of patients in a minority of cancers including colorectal, bladder and oesophageal. In addition, many studies have shown no impact of Tregs in patient outcome. Traditionally, research has identified Tregs as forkhead box P3 (FOXP3⁺) T cells in order to make such associations. Recently, it has become evident that regulatory populations are very heterogeneous, and this heterogeneity is essential for Treg function. Treg heterogeneity likely affects predictions of patient outcome, and different Treg populations may have different influences on tumours. The study of Tregs in cancer must include a better definition of the cells analysed. This review will focus primarily on colorectal cancer in humans, due to mixed data on the impact of Tregs on patient outcome in this disease.