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The significance of cytokine-producing B cells in breast tumor-draining lymph nodes

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Abstract

Purpose

The role of cytokine-producing B cells in antitumor immunity is mostly overlooked. In the present study, we investigated changes in B cell cytokine profiles in breast tumor-draining lymph nodes (TDLNs) during disease progression, and associations of these changes with prognostic indicators.

Methods

Flow cytometry was used to measure the expression of TNF-α, IL-10, TGF-β, IL-2 and IFN-γ in B cells from 42 axillary lymph nodes. The frequencies of IL-10+ and FoxP3+ T regulatory cells (Tregs) were also determined.

Results

No significant changes in B cell cytokine profiles were observed during breast cancer progression from stage I to III, but the percentage of B cells with high TNF-α expression (TNFhi) showed a negative relationship with lymph node involvement and Her2 expression (p < 0.05). The percentage of IL-10+ B cells was found to be significantly higher in non-metastatic lymph nodes in node-negative compared to node-positive patients (p = 0.001). The frequencies of IL-10+ and TNFhi B cells were found to be negatively correlated with the number of involved lymph nodes. The frequency of TNFhi B cells showed an inverse correlation with the frequency of FoxP3+ Tregs, which in turn was associated with indicators of a poor prognosis.

Conclusions

Our data indicate that the cytokine profiles of B cells in TDLNs of patients with breast cancer show associations with various disease parameters. TNFhi and IL-10+ B cells correlated positively with indicators of a good prognosis. Further functional studies are required to elucidate the role of cytokine production by B cells in immunity against breast cancer.

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Acknowledgements

This study was financially supported by grants from the Iran National Science Foundation (Grant No. 91004076), Shiraz Institute for Cancer Research (Grant No. ICR-100-508) and Shiraz University of Medical Sciences (Grant No. 91-6100). We thank K. Shashok (AuthorAID in the Eastern Mediterranean) for improving the text of the manuscript.

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Authors and Affiliations

  1. Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, P.O. Box: 71345-3119, Shiraz, Iran

    Fereshteh Mehdipour, Mahboobeh Razmkhah, Zahra Faghih & Abbas Ghaderi

  2. Department of Pathology, Shiraz Central Hospital, Shiraz, Iran

    Mandana Bagheri

  3. Breast Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Abdol-Rasoul Talei

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

    Abbas Ghaderi

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  1. Fereshteh Mehdipour
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  2. Mahboobeh Razmkhah
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  3. Zahra Faghih
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  5. Abdol-Rasoul Talei
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  6. Abbas Ghaderi
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Correspondence to Abbas Ghaderi.

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Mehdipour, F., Razmkhah, M., Faghih, Z. et al. The significance of cytokine-producing B cells in breast tumor-draining lymph nodes. Cell Oncol. 42, 381–395 (2019). https://doi.org/10.1007/s13402-019-00433-3

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