IL-17 and IL-4 producing CD8+ T cells in tumor draining lymph nodes of breast cancer patients: positive association with tumor progression

ABSTRACT

CD8+ cytotoxic T lymphocytes have been recently divided based on their cytokine expression profile. To evaluate the percentages of CD8+lymphocytes and their effector subsets including Tc1, Tc2 and Tc17 in the tumor draining lymph nodes [TDLNs] of patients with breast cancer. Single cell suspensions were obtained from TDLNs of 42 patients with breast cancer. Staining of the cell surface markers and intracellular cytokines was performed using appropriate fluorochrome-conjugated antibodies. The data was acquired on a four-color flow cytometer and was analyzed by CellQuestPro software package. The percentages of different CD8+ cell subtypes [Tc1, Tc2 and Tc17] were quantified in CD8+T lymphocytes. The comparison was made between LN+ versus LN- patients, as well as patients in different clinico-pathological status. The percentage of Tc1, Tc2 and Tc17 subsets were not significantly different between LN+ and LN- patients. Despite no difference in the percentages of Tc1 cells in LN+ patients with infiltrative ductal carcinoma [IDC], the mean expression of IFN-gamma by Tc1 cells decreased significantly in comparison to LN- patients. On the other hand, the percentages of Tc2 and Tc17 effector subsets were increased in advanced stages [p=0.018 and p=0.009, respectively]. As the first study to investigate various effector subtypes of CD8+ lymphocytes in TDLNs of patients with breast cancer, our data collectively suggests a positive association between IL-17- and IL-4-producing CD8+ T cell percentages [Tc2 and Tc17] in TDLNs with breast cancer progression. Although the number of Tc1 cells seems not to be affected by cancer progression, down-regulation of IFN-gamma by these cells seems to be associated with tumor metastasis to TDLNs. These findings may have implications in cancer immunotherapy based on CD8+ effector subsets.