il-17 and il-4 producing cd8+ t cells in tumor draining lymph nodes of breast cancer patients: positive association with tumor progression

background: cd8+ cytotoxic t lymphocytes have been recently divided based on their cytokine expression profile. objective: 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. methods: 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. results: 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-γ 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). conclusion: 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-γ 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.