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    Immune response in breast cancer brain metastases and their microenvironment: the role of the PD-1/PD-L axis

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    Author
    Duchnowska, R; Peksa, R; Radecka, B; Mandat, T; Trojanowski, T; Jarosz, B; Czartoryska-Arlukowicz, B; Olszewski, WP; Och, W; Kalinka-Warzocha, E; ...
    Date
    2016-04-27
    Source Title
    Breast Cancer Research
    Publisher
    BMC
    University of Melbourne Author/s
    Loi, Sherene
    Affiliation
    Sir Peter MacCallum Department of Oncology
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Duchnowska, R., Peksa, R., Radecka, B., Mandat, T., Trojanowski, T., Jarosz, B., Czartoryska-Arlukowicz, B., Olszewski, W. P., Och, W., Kalinka-Warzocha, E., Kozlowski, W., Kowalczyk, A., Loi, S., Biernat, W. & Jassem, J. (2016). Immune response in breast cancer brain metastases and their microenvironment: the role of the PD-1/PD-L axis. BREAST CANCER RESEARCH, 18 (1), https://doi.org/10.1186/s13058-016-0702-8.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/260579
    DOI
    10.1186/s13058-016-0702-8
    Abstract
    BACKGROUND: A better understanding of immune response in breast cancer brain metastases (BCBM) may prompt new preventive and therapeutic strategies. METHODS: Immunohistochemical expression of stromal tumor-infiltrating lymphocytes (TILs: CD4, CD8, CTLA4), macrophage/microglial cells (CD68), programmed cell death protein 1 receptor (PD-1), programmed cell death protein 1 receptor ligand (PD-L)1, PD-L2 and glial fibrillary acid protein was assessed in 84 BCBM and their microenvironment. RESULTS: Median survival after BCBM excision was 18.3 months (range 0-99). Median number of CD4+, CD8+ TILs and CD68+ was 49, 69 and 76 per 1 mm(2), respectively. PD-L1 and PD-L2 expression in BCBM was present in 53 % and 36 % of cases, and was not related to BCBM phenotype. PD-1 expression on TILs correlated positively with CD4+ and CD8+ TILs (r = 0.26 and 0.33), and so did CD68+ (r = 0.23 and 0.27, respectively). In the multivariate analysis, survival after BCBM excision positively correlated with PD-1 expression on TILs (hazard ratio (HR) = 0.3, P = 0.003), CD68+ infiltration (HR = 0.2, P < 0.001), brain radiotherapy (HR = 0.1, P < 0.001), endocrine therapy (HR = 0.1, P < 0.001), and negatively with hormone-receptor-negative/human epidermal growth factor receptor 2 (HER2)-positive phenotype of primary tumor (HR = 2.6, P = 0.01), HER2 expression in BCBM (HR = 4.9, P = 0.01). CONCLUSIONS: PD-L1 and PD-L2 expression is a common occurrence in BCBM, irrespective of primary tumor and BCBM phenotype. Favorable prognostic impact of PD-1 expression on TILs suggests a beneficial effect of preexisting immunity and implies a potential therapeutic role of immune checkpoint inhibitors in BCBM.

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