Clinical & Experimental Metastasis

, Volume 30, Issue 1, pp 69–81

Characterization of the inflammatory response to solid cancer metastases in the human brain

  • Anna Sophie Berghoff
  • Hans Lassmann
  • Matthias Preusser
  • Romana Höftberger
Research Paper

Abstract

New immunomodulatory agents showed promising activity in brain metastases (BM). However, little is known about the inflammatory response in BM. New insights are needed to further guide the development of treatment strategies. We investigated 17 human autoptic tissue specimens of BM from breast cancer (n = 3), non-small cell lung cancer (NSCLC; n = 5), small cell lung cancer (n = 3) and melanoma (n = 6). Immunohistochemical staining for a comprehensive panel of 21 inflammation-associated markers was performed. Results were quantified by manual counting of the various cell populations in three areas of 0.5 mm2 (intratumoral, peritumoral, control region). Profound microglia activation with marked peritumoral accumulation and some intratumoral infiltration of HLA-DR-positive microglia/macrophages was found. A high proportion of these cells showed strong immunoreactivity for phagocytosis associated markers and MHC class 1, while a smaller subgroup of cells expressed molecules involved in radical production. Only few B- and T-lymphocytes were observed in and around BM. The number of CD8-positive T-cells was not correlated to MHC class 1 expression on tumor cells and only a fraction of T-cells showed Granzym B expression. Melanoma BM had significantly less accumulation of peritumoral microglia than NSCLC BM. The inflammatory pattern was independent from treatment of patients with glucocorticoids or radiation. The inflammatory reaction to BM is mainly characterized by activation of microglia/macrophages and shows pronounced upregulation of markers involved in phagocytosis, but seem to be insufficient in activating adaptive immunity. Treatment strategies aimed at activating specific immunity may potentiate immune attack on tumor cells.

Keywords

Brain metastases Microglia Immune system Macrophages Lymphocytes Adaptive immune system Innate immune system 

Abbreviations

BM

Brain metastases

BRAF

v-RAF murine sarcoma viral oncogene homolog B1

CTL4

Anti cytotoxic T lymphocyte associated antigen 4

NSCLC

Non-small cell lung cancer

EGFR

Epithelial growth factor receptor

HER2

In human epidermal growth factor receptor 2

CNS

Central nervous system

SCLC

Small cell lung cancer

MHC II

Major histocompatibility antigen class II

MHC I

Major histocompatibility antigen class I

WBRT

Whole-brain radiation therapy

NO

Nitric oxide

APM

Antigen-processing machingery

TGF-beta

Transforming growth factor beta

GFAP

Glial fibrillary acidic protein

IBA-1

Ionized calcium binding adaptor molecule 1

AIF-1

Allograft inflammatory factor 1

SIGLEC-11

Sialic acid-binding Ig-like lectin 11

HMGB1

High-mobility group box 1

iNOS

Inducible nitric oxide synthase

NCF-1

Neutrophil cytosolic factor 1

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Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Anna Sophie Berghoff
    • 1
    • 3
  • Hans Lassmann
    • 4
  • Matthias Preusser
    • 2
    • 3
  • Romana Höftberger
    • 1
  1. 1.Institute of NeurologyMedical University of ViennaViennaAustria
  2. 2.Department of Medicine IMedical University of ViennaViennaAustria
  3. 3.Comprehensive Cancer Center, CNS UnitMedical University of ViennaViennaAustria
  4. 4.Center for Brain ResearchMedical University of ViennaViennaAustria

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