Immune regulatory cells and IL17-producing lymphocytes in patients with benign and malignant salivary gland tumors

• Increase of Treg cells and CTLA4+ CD4+ lymphocytes in salivary gland tumors.
• Decrease in Th17 cells in patients with malignant SG tumors comparing to controls.
• Lower Th17/Treg ratio in malignant and benign SG tumors in comparison to controls.
• Higher expression intensity of IL17 by Tc17 cells in malignant SG tumors.

The relationship between salivary gland tumors and immune system has not been well inspected. We aimed to investigate the distribution of CD4+CD25+Foxp3+ regulatory T (Treg) cells, CTLA4+CD4+ lymphocytes, as well asIL-17 producing CD4+ and CD8+ (Th17 and Tc17) lymphocytes in peripheral blood of patients with benign and malignant salivary gland tumors and a group of healthy controls. Peripheral blood samples were obtained from 27 patients with salivary gland tumors (19 benign and 8 malignant; mean age of 49.2 ± 18.3), as well as19 age/sex matched healthy donors. Fluorochrome-conjugated antibodies were used to stain the cell surface markers, as well as intracellular molecules following cell-membrane fixation and permeabilization. The stained cells were acquired on a FACSCalibur four-color flowcytometer and analyzed by CellQuest Pro software package. The data were presented as mean percentages ± SEM. Results indicated that the patients with malignant salivary gland tumors have increased percentage of Treg cells (7.74 ± 1.1) and intracellular CTLA4 (inCTLA4)-positive CD4+ lymphocytes (8.18 ± 1.77) in comparison to the patients with benign tumors (4.38 ± 0.56 for Treg cells and 3.83 ± 0.56 for CTLA4+CD4+ cells), as well as control subjects (2.34 ± 0.28 for Treg cells and 2.22 ± 0.25 for CTLA4+CD4+ cells) (p ≤ 0.001). Conversely these patients had reduced percentage of Th17 cells (0.84 ± 0.14) comparing to the patients with benign tumors (2.09 ± 0.31) as well as control subjects (2.31 ± 0.23) (p ≤ 0.001). In addition, the ratio of Th17/Treg lymphocytes was significantly lower in both malignant (0.12 ± 0.03) and benign (0.48 ± 0.09) tumors in comparison to control subjects (1.26 ± 0.23) (p < 0.001). The mean percentage of Tc17 cells in patients with benign (1.14 ± 0.15) and malignant (0.60 ± 0.13) tumors was nearly similar to those in control subjects (0.83 ± 0.14) but the mean expression intensityofIL-17 by these cells was significantly higher in patients with malignant tumors (11.06 ± 1.26) than controls (7.61 ± 0.69) (p = 0.01). Increase in the prevalence of regulatory lymphocytes, Treg cells and CTLA4+CD4+ lymphocytes, as well as the imbalance of Th17/Treg ratio may suggest the contribution of these immune effector cells in the progression of salivary gland tumors. From immune-regulatory point of view, these data also suggest that benign salivary gland tumors might fall between healthy and malignant conditions. The immunity to salivary gland tumors, as well as the findings presented here merits more in-depth investigation.