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Breast Cancer
Published in: Breast Cancer 2/2019

01-03-2019 | Original Article

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

Authors: Emi Ishigami, Masahiro Sakakibara, Junta Sakakibara, Takahito Masuda, Hiroshi Fujimoto, Shouko Hayama, Takeshi Nagashima, Takafumi Sangai, Ayako Nakagawa, Yukio Nakatani, Masayuki Otsuka

Published in: Breast Cancer | Issue 2/2019

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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.
Appendix
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Metadata
Title
Coexistence of regulatory B cells and regulatory T cells in tumor-infiltrating lymphocyte aggregates is a prognostic factor in patients with breast cancer
Authors
Emi Ishigami
Masahiro Sakakibara
Junta Sakakibara
Takahito Masuda
Hiroshi Fujimoto
Shouko Hayama
Takeshi Nagashima
Takafumi Sangai
Ayako Nakagawa
Yukio Nakatani
Masayuki Otsuka
Publication date
01-03-2019
Publisher
Springer Japan
Published in
Breast Cancer / Issue 2/2019
Print ISSN: 1340-6868
Electronic ISSN: 1880-4233
DOI
https://doi.org/10.1007/s12282-018-0910-4

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