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