Hyaluronan-Binding T Regulatory Cells in Peripheral Blood of Breast Cancer Patients

Regulatory T cells (Treg), both natural and induced, play an important role in maintaining immune homeostasis. Alterations in the number and functions of Tregs are involved in tumor growth. One of the possible regulatory mechanisms of Treg functional activity involves interaction with major component of extracellular matrix hyaluronan. It has been demonstrated that high molecular weight hyaluronan promotes Treg function via increased expression of FoxP3 and production of IL-10. Moreover, previous research has shown highly enhanced suppressor function of hyaluronan-binding CD4+CD25+ Tregs in mice. Breast cancer is characterized by upregulated production of tumor-associated hyaluronan, therefore we investigated hyaluronan-binding subset of Tregs obtained from peripheral blood of breast cancer patients. As a result, we showed that the majority of peripheral blood Tregs were able to adhere to immobilized hyaluronan, and these cells exerted superior suppressor activity, suggesting a key role in regulatory functions of these cells. The percentage of CD4+FoxP3+ Treg cells binding hyaluronan, as well as CD39+ hyaluronan-binding Tregs were significantly increased in breast cancer patients compared to healthy donors. Enhanced number of the activated Treg cells might play an important role in the suppression of antitumor immunity.