Research Papers:

Comparison of immune microenvironments between primary tumors and brain metastases in patients with breast cancer

Rin Ogiya, Naoki Niikura _, Nobue Kumaki, Hiroyuki Yasojima, Tsutomu Iwasa, Chizuko Kanbayashi, Risa Oshitanai, Michiko Tsuneizumi, Ken-ichi Watanabe, Akira Matsui, Tomomi Fujisawa, Shigehira Saji, Norikazu Masuda, Yutaka Tokuda and Hiroji Iwata

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Oncotarget. 2017; 8:103671-103681. https://doi.org/10.18632/oncotarget.22110

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Rin Ogiya1, Naoki Niikura1, Nobue Kumaki2, Hiroyuki Yasojima3, Tsutomu Iwasa4, Chizuko Kanbayashi5, Risa Oshitanai1, Michiko Tsuneizumi6, Ken-ichi Watanabe7, Akira Matsui8, Tomomi Fujisawa9, Shigehira Saji10, Norikazu Masuda3, Yutaka Tokuda1 and Hiroji Iwata11

1Department of Breast and Endocrine Surgery, Tokai University School of Medicine, Kanagawa, Japan

2Department of Pathology, Tokai University School of Medicine, Kanagawa, Japan

3Department of Surgery, Breast Oncology, National Hospital Organization Osaka National Hospital, Osaka, Japan

4Department of Medical Oncology, Kindai University School of Medicine, Osaka, Japan

5Department of Breast Oncology, Niigata Cancer Center Hospital, Niigata, Japan

6Department of Breast Surgery, Shizuoka General Hospital, Shizuoka, Japan

7Department of Breast Surgery, Hokkaido Cancer Center, Sapporo, Japan

8Department of Surgery, National Hospital Organization, Tokyo Medical Center, Tokyo, Japan

9Department of Breast Oncology, Gunma Prefectural Cancer Center, Gunma, Japan

10Department of Medical Oncology, Fukushima Medical University, Fukushima, Japan

11Department of Breast Oncology, Aichi Cancer Center Hospital, Nagoya, Japan

Correspondence to:

Naoki Niikura, email: [email protected]

Keywords: breast cancer, brain metastases, tumor infiltrating lymphocytes, PD-L1, immune microenvironment

Received: July 11, 2017     Accepted: September 20, 2017     Published: October 27, 2017


Background: Immune checkpoint inhibitors are reported to be effective in patients with brain metastases. However, detailed characteristics of the brain metastasis immune microenvironment remain unexplored.

Results: The median tumor-infiltrating lymphocyte (TIL) category in brain metastases was 5% (1–70%). In 46 pair-matched samples, the percentages of TILs were significantly higher in primary breast tumors than in brain metastases (paired t-test, P < 0.01). The numbers of CD4/CD8/Foxp3-positive cells were significantly higher in primary breast tumors than in brain metastases (paired t-test, P < 0.05 for all antibodies). In patients with triple-negative breast cancer specifically, low TIL numbers were associated with significantly shorter overall survival compared to high TIL numbers (log-rank test, P = 0.04).

Materials and Methods: We retrospectively identified 107 patients with breast cancer and brain metastases who had undergone surgery between 2001 and 2012 at 8 institutions, and collected 191 samples including brain metastases alone and primary tumors with pair-matched brain metastasis samples. Hematoxylin and eosin-stained slides were evaluated for TILs and categorized according to the extent of staining. Immunohistochemistry for CD4, CD8, Foxp3, PD-L1, PD-L2, and HLA class I was also performed.

Conclusions: There are significantly fewer TILs in brain metastases than in primary breast tumors.

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