Memory CD4 T cell subsets in tumor draining lymph nodes of breast cancer patients: A focus on T stem cell memory cells.

Background: The compartments of memory T cells play a fundamental role in the immune system by substantiating specific and acquired immunity. A new subset of memory cells, T stem cell memory (T) cells, with stem cell-like properties, a high capacity to proliferate, a long survival, and an ability to differentiate into all effector and memory cells has recently been introduced. In the present study, we aimed to determine the frequency of CD4 T and other T memory cell subsets in tumor draining lymph nodes of breast cancer patients. Materials and methods: Mononuclear cells were obtained from axillary lymph nodes of 52 untreated patients with breast cancer (BC) and stained with fluorochrome conjugated anti-CD4, −CCR7, −CD45RO and -CD95 antibodies to detect different subtypes of memory cells in CD4 lymphocyte populations. Data were acquired using a four-color FACSCalibur flow cytometer and analyzed using CellQuest Pro software. Results: We found that >70% of CD4 lymphocytes in draining lymph nodes of BC patients exhibited a memory phenotype of which 7.04 ± 1.04% had a T phenotype (CD4CCR7CD45ROCD95). The frequency of T cells was significantly higher in tumor positive lymph nodes compared to tumor negative lymph nodes ( p = 0.026) as well as among those patients who had at least one affected lymph node ( p = 0.012). Moreover, we found that the total frequency of central memory T cells (T) with a low expression of CD45RO was significantly higher among these patients. The percentage of CD45RO T cells was also found to increase with tumor progression from stage I to stage III ( p = 0.020). On the other hand, we found that the percentage of CD95 effector memory T cells (T) was significantly decreased in involved lymph nodes ( p = 0.009). Conclusion: Our data suggest that following long-term exposure to putative tumor antigens, T cells proliferate to generate a pool of committed memory and effector T cells. As the tumor progresses, the immunosuppressive milieu induced by tumor cells may slow down the differentiation of CD45RO T cells to more functional sub-populations. [ABSTRACT FROM AUTHOR]