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

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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.

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Funding

This study was financially supported by grants from the Shiraz University of Medical Sciences, Shiraz, Iran [Grant No. 94–7484] and Shiraz Institute for Cancer Research [ICR-100-500], and was part of an MSc thesis written by Yasmin Vahidi.

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Author notes

  1. Yasmin Vahidi and Zahra Faghih contributed equally to this study.

Authors and Affiliations

  1. Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Yasmin Vahidi, Zahra Faghih & Abbas Ghaderi

  2. Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Yasmin Vahidi, Mehrnoosh Doroudchi & Abbas Ghaderi

  3. Breast Disease Research Center, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Abdol-Rasoul Talei

Authors
  1. Yasmin Vahidi
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Corresponding author

Correspondence to Abbas Ghaderi.

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures used involving human participants were in accordance with the ethical standards of the Ethical Committee of Shiraz University of Medical Sciences and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all participants included in the study.

Electronic supplementary material

Supplementary Fig. 1.

Frequency of TEM in TDLNs of breast cancer patients with positive and negative progesterone receptor (PR) tumors. The mean expression of CD95 on CD95HiTEM cells in patients with progesterone receptor expressing tumors (PR+) in comparison to PR negative ones. The data are presented as mean ± SEM. *Difference significant at 0.05 level (2-tailed). (DOCX 64.6 kb)

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Vahidi, Y., Faghih, Z., Talei, AR. et al. Memory CD4+ T cell subsets in tumor draining lymph nodes of breast cancer patients: A focus on T stem cell memory cells. Cell Oncol. 41, 1–11 (2018). https://doi.org/10.1007/s13402-017-0352-6

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  • DOI: https://doi.org/10.1007/s13402-017-0352-6

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