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. 2018 Feb;41(1):1-11.
doi: 10.1007/s13402-017-0352-6. Epub 2017 Oct 9.

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

Yasmin Vahidi  1   2 , Zahra Faghih  1 , Abdol-Rasoul Talei  3 , Mehrnoosh Doroudchi  2 , Abbas Ghaderi  4   5
Affiliations

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

Yasmin Vahidi et al. Cell Oncol (Dordr). 2018 Feb.

Abstract

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 (TSCM) 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+ TSCM 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 TSCM phenotype (CD4+CCR7+CD45RO-CD95+). The frequency of TSCM 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 (TCM) with a low expression of CD45RO was significantly higher among these patients. The percentage of CD45ROLow TCM 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 CD95Hi effector memory T cells (TEM) was significantly decreased in involved lymph nodes (p = 0.009).

Conclusion: Our data suggest that following long-term exposure to putative tumor antigens, TSCM 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 CD45ROLow TCM cells to more functional sub-populations.

Keywords: Breast cancer; CD4+ T stem cell memory cells; Lymph node.

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