Immune microenvironment in brain metastases of breast cancer.

Abstract

1081 Background: In patients with brain metastasis (BM) of melanoma or lung cancer, significant activity of immune checkpoint inhibitors has been reported. However, details of the immune microenvironment in BM has not been unveiled. In this study, we used immunohistochemistry (IHC) to compare primary breast tumors and BM tumor samples with respect to tumor infiltrating lymphocytes (TILs) and tumor characteristics related to the immune system. Methods: We retrospectively identified 107 patients with breast cancer, diagnosed with BM, who had undergone surgery between 2001 and 2012 at 8 institutions. We collected 191 samples which included both BM samples alone and pair-matched samples (primary and BM). Hematoxylin and eosin (H&E) stained slides were evaluated for stromal TILs in 10% increments (0–1%, > 1– < 10%, 10%–100%). IHC was performed using the following primary antibodies: CD4, CD8, Foxp3, PD-L1, PD-L2 and HLA class I. The cells positive for each antibody signal were counted automatically using ImageJ (NIH). The expression of PD-L1, PD-L2, and HLA on the tumor cells was scored as 0 (negative), 1 (weak or focal), or 2 (strong). Results: The median category of TILs of BM tumors was > 1– < 10% (range: 1–30%). Forty-six pair-matched samples were analyzed and the percentage of TILs in the primary breast tumor was significantly higher than that in BM samples (paired t-test, P < 0.01). The number of CD4/CD8/Foxp3 positive cells in primary breast tumor was also significantly higher than in BM samples (paired t-test, P < 0.05 for all categories). The negative/positive conversion occurred with the expression of HLA/PD-L2 on tumor cells (paired t-test, P = 0.03/0.06, respectively). No significant difference was observed in the overall survival (OS) of patients, from initial BM, based on high or low TILs (log-rank test, P = 0.131). However, triple negative breast cancer patients with low TILs had significantly shorter OS compared with patients with high TILs (log-rank test, P = 0.04). Conclusions: We demonstrated that TILs in BM tumors was significantly lower as compared to primary breast tumors. The expression of immune related molecules on tumor cells was converted in BM tumors.