Journal d'immunologie clinique et cellulaire
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Hyaluronan-Binding T Regulatory Cells in Peripheral Blood of Breast Cancer Patients

Yuliya Perfilyeva, Yekaterina Ostapchuk, Esin Aktas Cetin, Abdullah Yilmaz, Gunnur Deniz, Shynar Talaeva, Nazgul Omarbaeva, Igor Oskolchenko and Nikolai Belyaev

Regulatory T cells (T_reg), both natural and induced, play an important role in maintaining immune homeostasis. Alterations in the number and functions of T_regs are involved in tumor growth. One of the possible regulatory mechanisms of T_reg functional activity involves interaction with major component of extracellular matrix hyaluronan. It has been demonstrated that high molecular weight hyaluronan promotes T_reg 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⁺ T_regs in mice. Breast cancer is characterized by upregulated production of tumor-associated hyaluronan, therefore we investigated hyaluronan-binding subset of T_regs obtained from peripheral blood of breast cancer patients. As a result, we showed that the majority of peripheral blood T_regs 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⁺ T_reg cells binding hyaluronan, as well as CD39⁺ hyaluronan-binding T_regs were significantly increased in breast cancer patients compared to healthy donors. Enhanced number of the activated T_reg cells might play an important role in the suppression of antitumor immunity.