Abstract
Background
Human immunological memory is a hallmark of the adaptive immune system and plays an important role in the development of effective immune responses against tumors. In the present study, we aimed to determine the frequencies of CD8 + memory T cell subsets including stem memory T cells (TSCM) in tumor-draining lymph nodes of patients with breast cancer (BC).Methods
Mononuclear cells were obtained from axillary lymph nodes of 52 untreated patients with BC and stained for CD8, CCR7, CD45RO, CD95 markers to detect different subtypes of memory cells in the CD8 + lymphocyte population. Data were acquired with four-color flow cytometry and analyzed with CellQuest Pro software.Results
We observed that 47.65±2.66 of CD8+ lymphocytes expressed the CD45RO marker for memory T cells. Statistical analysis showed that the total frequency of central memory T cells (TCM) and their subset with low CD45RO expression was significantly higher in tumor-involved nodes compared to tumor-free ones (P=0.024 and P=0.017, respectively). Mean CD96 expression (based on mean fluorescence intensity) on the surface of TCM, their CD45RO hi TCM and CD45RO low subsets, and TSCM was higher in patients with stage II compared to those with stage I disease (P<0.05). The percentage of naive CD8 + T cells was significantly higher in tumor-involved lymph nodes compared to tumor-free ones (P=0.025).Conclusions
Our data collectively indicate no significant differences in the frequencies of CD8 + lymphocytes or their memory T cell subsets in tumor-draining lymph nodes of patients with BC. However, the frequency of CD45 low TCM along with naive CD8 + lymphocytes was higher in tumor-involved nodes, which suggests that after long-term exposure to the antigen, and despite the immune reaction in order to provide a pool of effective memory cells, memory cell differentiation is blocked in early-stage (CD45RO low ) due to tumor-derived suppressive factors. Identifying the molecular and cellular mechanisms behind this suppression can provide invaluable tools for adoptive T cell therapies in cancer.