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Coexistence of regulatory B cells and regulatory T cells in tumor-infiltrating lymphocyte aggregates is a prognostic factor in patients with breast cancer

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Abstract

Background

Tumors can acquire tolerance to tumor immunity and develop enhanced proliferation. Regulatory B cells (Bregs), whose role in immune tolerance is similar to that of regulatory T cells (Tregs), appear to be involved in tumor immunity. Recently, Bregs were found to induce Tregs against tumor immunity. However, the platform for the coexistence of Bregs and Tregs in cancer patients and its clinical significance remain unclear; thus, they were evaluated in breast cancer patients.

Methods

In 489 breast cancer patients, CD25- and IL10-positive Bregs and Foxp3-positive Tregs were immunohistochemically evaluated in tumor-infiltrating lymphocyte aggregates (TIL aggregates) that consisted of CD19-positive B-cell follicles and CD3-positive T-cell parafollicles. Then the correlations of the localization and existence of these cells with metastasis-free survival (MFS) were evaluated in breast cancer patients.

Results

TIL aggregates were observed in marginal regions of tumors in breast cancer patients. In the TIL aggregates, the existence of Bregs was closely related to that of Tregs (p < 0.0001). On multivariate analysis, the coexistence of Bregs and Tregs in TIL aggregates was correlated with MFS in breast cancer patients (p = 0.007). Furthermore, MFS was significantly shorter for patients with the coexistence of Tregs and Bregs in TIL aggregates than in those with Tregs alone without Bregs (p = 0.0475).

Conclusions

The present results suggest that Bregs are related to the induction of Tregs in TIL aggregates and the development of metastasis of breast cancer cells. Bregs are expected to be a new diagnostic and therapeutic target in breast cancer patients.

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Acknowledgements

The authors would like to thank the patients, nurses, and physicians at Chiba University Hospital. This work was greatly assisted by the excellent technical help and advice of Hiroko Kawamura.

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Authors and Affiliations

  1. Department of General Surgery, Chiba University Graduate School of Medicine, Chiba, Chiba, Japan

    Emi Ishigami, Junta Sakakibara, Takahito Masuda, Hiroshi Fujimoto, Shouko Hayama, Takeshi Nagashima, Takafumi Sangai, Ayako Nakagawa & Masayuki Otsuka

  2. Department of Breast Surgery, International University of Health and Welfare Hospital, Nasushiobara, Tochigi, Japan

    Masahiro Sakakibara

  3. Diagnostic Pathology, Chiba University Graduate School of Medicine, Chiba, Chiba, Japan

    Yukio Nakatani

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  1. Emi Ishigami
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  2. Masahiro Sakakibara
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Correspondence to Masahiro Sakakibara.

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Ishigami, E., Sakakibara, M., Sakakibara, J. et al. Coexistence of regulatory B cells and regulatory T cells in tumor-infiltrating lymphocyte aggregates is a prognostic factor in patients with breast cancer. Breast Cancer 26, 180–189 (2019). https://doi.org/10.1007/s12282-018-0910-4

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  • DOI: https://doi.org/10.1007/s12282-018-0910-4

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