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

Autor: Duchnowska R; Department of Oncology, Military Institute of Medicine, Szaserów St 128, 04-141, Warsaw, Poland. rdtt@wp.pl., Pęksa R; Department of Pathology, Medical University of Gdańsk, 7 Dębinki St, 80-211, Gdańsk, Poland., Radecka B; Department of Oncology, Regional Oncology Center, 66a Katowicka St, 45-060, Opole, Poland., Mandat T; Department of Neurosurgery, Oncology Center-Institute, 5 Roentgena St, 02-781, Warsaw, Poland., Trojanowski T; Department of Neurosurgery, Medical University of Lublin, 1 Al. Racławickie, 20-059, Lublin, Poland., Jarosz B; Department of Neurosurgery, Medical University of Lublin, 1 Al. Racławickie, 20-059, Lublin, Poland., Czartoryska-Arłukowicz B; Department of Oncology, Regional Oncology Center, 12 Ogrodowa St, 15-027, Białystok, Poland., Olszewski WP; Department of Pathology, Oncology Center-Institute, 5 Roentgena St, 02-781, Warsaw, Poland., Och W; Department of Neurosurgery, Regional Hospital, 18 Żołnierska St, 10-561, Olsztyn, Poland., Kalinka-Warzocha E; Department of Oncology, Regional Oncology Center, 62 Pabianicka St, 93-513, Łódź, Poland., Kozłowski W; Department of Pathology, Military Institute of Medicine, Szaserów St 128, 04-141, Warsaw, Poland., Kowalczyk A; Department of Oncology and Radiotherapy, Medical University of Gdańsk, 7 Dębinki St, 80-211, Gdańsk, Poland., Loi S; Division of Cancer Medicine and Research, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett Street, East Melbourne, VIC, 8006, Australia., Biernat W; Department of Pathology, Medical University of Gdańsk, 7 Dębinki St, 80-211, Gdańsk, Poland., Jassem J; Department of Oncology and Radiotherapy, Medical University of Gdańsk, 7 Dębinki St, 80-211, Gdańsk, Poland.
Jazyk: angličtina
Zdroj: Breast cancer research : BCR [Breast Cancer Res] 2016 Apr 27; Vol. 18 (1), pp. 43. Date of Electronic Publication: 2016 Apr 27.
DOI: 10.1186/s13058-016-0702-8
Abstrakt: 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.
Databáze: MEDLINE
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