CD45RA^-Foxp3^high regulatory T cells have a negative impact on the clinical outcome of head and neck squamous cell carcinoma

Background: Although regulatory T cells (Tregs) are thought to play an important role in immune suppression, their clinical significance in head and neck squamous cell carcinoma (HNSCC) is unclear. A recent study reported Tregs could be divided into functional subsets based on the expression of CD45RA and Foxp3.

Method: The frequency of circulating Treg subsets was analyzed in patients with HNSCC and compared with the frequency in patients with benign tumors. The association of Treg subsets with the frequency of lymphocyte subsets, status of progression, clinical course, and prognosis were also examined.

Results: The frequency of CD4⁺Foxp3⁺ Tregs was comparable between HNSCC patients and age-matched benign tumor patients; however, CD45RA^-Foxp3^high Tregs were significantly increased in HNSCC patients, in particular those with advanced stage tumors. The high frequency of CD45RA^-Foxp3^high Tregs correlated with a poor prognosis and the low frequency of CD45RA^-Foxp3^high Tregs before treatment showed a better clinical outcome, even in patients with advanced stage tumors. CD45RA^-Foxp3^high Treg numbers were decreased after intensive treatments; however, Treg numbers recovered in the early stages of recurrent cases, even before the clinical manifestation.

Conclusion: CD45RA^-Foxp3^high Tregs are associated with the clinical course of HNSCC and might be a new target for treatment and an early marker of tumor recurrence in HNSCC patients.