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Breast Cancer Research
Published in: Breast Cancer Research 1/2016

Open Access 01-12-2016 | Research article

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

Authors: Renata Duchnowska, Rafał Pęksa, Barbara Radecka, Tomasz Mandat, Tomasz Trojanowski, Bożena Jarosz, Bogumiła Czartoryska-Arłukowicz, Wojciech P. Olszewski, Waldemar Och, Ewa Kalinka-Warzocha, Wojciech Kozłowski, Anna Kowalczyk, Sherene Loi, Wojciech Biernat, Jacek Jassem, for the Polish Brain Metastasis Consortium

Published in: Breast Cancer Research | Issue 1/2016

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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 mm2, 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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Metadata
Title
Immune response in breast cancer brain metastases and their microenvironment: the role of the PD-1/PD-L axis
Authors
Renata Duchnowska
Rafał Pęksa
Barbara Radecka
Tomasz Mandat
Tomasz Trojanowski
Bożena Jarosz
Bogumiła Czartoryska-Arłukowicz
Wojciech P. Olszewski
Waldemar Och
Ewa Kalinka-Warzocha
Wojciech Kozłowski
Anna Kowalczyk
Sherene Loi
Wojciech Biernat
Jacek Jassem
for the Polish Brain Metastasis Consortium
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2016
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-016-0702-8

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