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

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-SCM) 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-SCM and other T memory cell subsets in tumor draining lymph nodes of breast cancer patients. 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. 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-SCM phenotype (CD4(+)CCR7(+)CD45RO(-)CD95(+)). The frequency of T-SCM 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-CM) with a low expression of CD45RO was significantly higher among these patients. The percentage of CD45RO(Low) T-CM 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(Hi) effector memory T cells (T-EM) was significantly decreased in involved lymph nodes (p = 0.009). Our data suggest that following long-term exposure to putative tumor antigens, T-SCM 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(Low) T-CM cells to more functional sub-populations.