JJW executed the MTT assays, FOXO3a overexpression experiments and statistical analysis. ZYL fulfilled MTT and Western Blot analysis. LLL and WYW coordinated and provided important suggestions including some agents, and critical read the manuscript. All authors read and approved the final manuscript.”
“Background Globally, head and neck cancer is the sixth most common type of cancer [1]. Approximately 90% of head and neck cancer cases arise from organs SB-715992 cell line lined by squamous epithelium [2]. Despite new treatment modalities (including surgical and adjuvant chemoradiotherapy) and their success in terms of overall quality of life, survival rates for this disease have not

improved in the past 30 years [3]. It is widely recognized that the progression of head and neck squamous cell carcinoma (HNSCC) is attributed to the peripheral immune tolerance to tumors [4]. Foxp3+CD25+CD4+ T FK228 price regulatory cells (Tregs), with immunosuppressive activity SN-38 solubility dmso against tumor-specific T cell responses, are one of the crucial players for immune tolerance [5, 6]. To date, Tregs have been shown to be elevated in a number of different

cancers [7–13], including HNSCC where it has been reported that Tregs increase in the peripheral circulation when compared with healthy donors. However, Tregs are not functionally homogeneous [14]. For example, Zhou et al. [15] showed that CD4+Foxp3- T cells could transiently express lower levels of Foxp3 and leads to the generation of pathogenic memory T cells. Allan et al. [16] postulated that activated CD4+ T cells, but without regulatory activity, could express Foxp3. Hence, identification of distinct Treg subsets and their functional abilities might be more intriguing in antitumor immunity field. Recently, Sakaguchi’s group demonstrated that human Tregs can be dissected into three functionally distinct

subsets on the basis of CD45RA, Foxp3 and CD25 expression: CD45RA+Foxp3low Tregs (resting Tregs), which are CD25++, CD45RA-Foxp3high Tregs (activated Tregs), which are CD25+++, and CD45RA-Foxp3lowCD4+ T cells (cytokine-secreting non-suppressive T cells), which are CD25++[14]. Avelestat (AZD9668) Based on this classification of human Tregs, subsequent studies showed that the frequency and function of these Treg subsets vary in different disease models, including systemic lupus erythematosus, sarcoidosis, and aplastic anemia [14, 17, 18]. However, the characterizations of these functionally distinct Treg subsets in HNSCC are unknown. When assessing the Treg subsets it is important not only to examine their characteristics in HNSCC patients as a whole cohort, but also to investigate their variations in patients with HNSCC developing from different anatomic subsites, as the various subsites of HNSCC are known to have different etiology and survival rates.