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

// Rin Ogiya 1 , Naoki Niikura 1 , Nobue Kumaki 2 , Hiroyuki Yasojima 3 , Tsutomu Iwasa 4 , Chizuko Kanbayashi 5 , Risa Oshitanai 1 , Michiko Tsuneizumi 6 , Ken-ichi Watanabe 7 , Akira Matsui 8 , Tomomi Fujisawa 9 , Shigehira Saji 10 , Norikazu Masuda 3 , Yutaka Tokuda 1 and Hiroji Iwata 11 1 Department of Breast and Endocrine Surgery, Tokai University School of Medicine, Kanagawa, Japan 2 Department of Pathology, Tokai University School of Medicine, Kanagawa, Japan 3 Department of Surgery, Breast Oncology, National Hospital Organization Osaka National Hospital, Osaka, Japan 4 Department of Medical Oncology, Kindai University School of Medicine, Osaka, Japan 5 Department of Breast Oncology, Niigata Cancer Center Hospital, Niigata, Japan 6 Department of Breast Surgery, Shizuoka General Hospital, Shizuoka, Japan 7 Department of Breast Surgery, Hokkaido Cancer Center, Sapporo, Japan 8 Department of Surgery, National Hospital Organization, Tokyo Medical Center, Tokyo, Japan 9 Department of Breast Oncology, Gunma Prefectural Cancer Center, Gunma, Japan 10 Department of Medical Oncology, Fukushima Medical University, Fukushima, Japan 11 Department of Breast Oncology, Aichi Cancer Center Hospital, Nagoya, Japan Correspondence to: Naoki Niikura, email: niikura@is.icc.u-tokai.ac.jp Keywords: breast cancer, brain metastases, tumor infiltrating lymphocytes, PD-L1, immune microenvironment Received: July 11, 2017      Accepted: September 20, 2017      Published: October 27, 2017 ABSTRACT 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.