Although the frequency of CD45RA-Foxp3high Tregs did not differ between patients with HPSCC, NPSCC, OPSCC, and LSCC, it was found that HNSCC patients with advanced stage tumors and those that metastasized to the lymph nodes had significantly increased levels of CD45RA-Foxp3high Tregs in LGX818 clinical trial comparison to patients with early stage tumors and no nodal involvement, respectively; in contrast to previous HNSCC studies which found

no differences [10, 22–24]. However, recent studies of HNSCC showed that CD127low/- Tregs (including CD4+CD25interCD127low/- and CD4+CD25high CD127low/- Tregs) or CD4+CD25+Foxp3+ Tregs are associated with advanced stage and nodal involvement [33, 34]. This is hypothesized to be due to the different see more phenotypes used to identify Tregs and the composition of the patient cohorts.

Conclusions The present study provides evidence to support the notion of heterogeneous Treg subsets in the peripheral circulation of HNSCC patients. CD45RA-Foxp3high Tregs (one distinct Treg subset) significantly increase in the peripheral circulation of HNSCC click here patient subgroups. Importantly, CD45RA-Foxp3high Tregs positively correlate with tumor progression. The present findings provide important information of the future design of immunotherapeutic strategies for HNSCC patients, for example by monoclonal antibodies (anti-PD-1 Ab and anti-CTLA-4 Ab), to reduce the expansion, survival and suppressive function of the Tregs responsible for HNSCC-specific immune suppression – as ever the problem

remains effective, specific targeting. Acknowledgements This work was supported by the National Natural Science Foundation of China (Grant No. 81271055/H1301). Electronic supplementary material Additional file 1: Figure S1: Relationship between expression levels of CD25 vs. CD45RA and Foxp3 vs. CD45RA in PB CD4+ mafosfamide T cells of HNSCC patients. The degree of CD25 expression in CD45RA + CD25++ Tregs (Fraction 1), CD45RA-CD25+++ Tregs (Fraction 2), and CD45RA-CD25++CD4+ T cells (Fraction 3). (a) are proportional to Foxp3 expression in CD45RA + Foxp3low Tregs (Fraction I), CD45RA-Foxp3high Tregs (Fraction II), and CD45RA-Foxp3low CD4+ T cells (Fraction III), respectively (b). Gating strategy used is illustrated as follows: CD45RA-CD25+ cells with red background fluorescence (x-axis) were defined as CD45RA-CD25+ (CD25low). The CD45RA + CD25++ (CD25inter) gate (Fraction 1) was adjusted to contain CD45RA + T cells that express CD25 more brightly than CD45RA-CD25+ (CD25low). The CD45RA-CD25+++ (CD25high) gate (Fraction 2) was adjusted to contain CD45RAT cells exceeding the level of CD25 expression on CD45RA + CD25++ (CD25inter) cells. The CD45RA-CD25++ (CD25inter) gate (Fraction 3) was adjusted to contain CD45RAT cells with the same level of CD25 expression as CD45RA + CD25++ (CD25inter) cells. (PDF 104 KB) Additional file 2: Figure S2: Cytokine production by responder T cells.