期刊
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
卷 44, 期 2, 页码 185-206出版社
WILEY
DOI: 10.1111/nan.12428
关键词
CD204; glioblastoma; glioma; macrophages; microglia; prognosis
资金
- Danish Council for Independent Research [4183-00183]
- Odense University Hospital Research Funds
- University of Southern Denmark
- Danish Cancer Research Foundation
- Oda and Hans Svenningsen's Foundation
- Krista and Viggo Petersen's Foundation
- Brodrene Hartmann's Foundation
- Knud and Edith Eriksen's Memorial Foundation
- Eva and Henry Fraenkel's Memorial Foundation
- Aase and Ejner Danielsen's Foundation
Aims: Glioblastomas are highly aggressive and treatment resistant. Increasing evidence suggests that tumour-associated macrophages/microglia (TAMs) facilitate tumour progression by acquiring a M2-like phenotype. Our objective was to investigate the prognostic value of TAMs in gliomas using automated quantitative double immunofluorescence. Methods: Samples from 240 patients with primary glioma were stained with antibodies against ionized calcium-binding adaptor molecule-1 (IBA-1) and cluster of differentiation 204 (CD204) to detect TAMs and M2-like TAMs. The expression levels were quantified by software-based classifiers. The associations between TAMs, gemistocytic cells and glioblastoma subtype were examined with immuno-and haematoxylin-eosin stainings. Three tissue arrays containing glioblastoma specimens were included to study IBA-1/CD204 levels in central tumour and tumour periphery and to characterize CD204 + cells. Results: Our data revealed that the amount of especially CD204(+) TAMs increases with malignancy grade. In grade III-IV, high CD204 expression was associated with shorter survival, while high IBA-1 intensity correlated with a longer survival. In grade IV, CD204 showed independent prognostic value when adjusting for clinical data and the methylation status of O6-methylguanine-DNA methyltransferase. Our findings were confirmed in two bioinformatics databases. TAMs were more abundant in central tumour tissue, mesenchymal glioblastomas and gliomas with many gemistocytic cells. CD204(+) TAMs coexpressed proteins related to tumour aggressiveness including matrix metallopeptidase-14 and hypoxiainducible factor-1 alpha. Conclusions: This is the first study to use automated quantitative immunofluorescence to determine the prognostic impact of TAMs. Our results suggest that M2-like TAMs hold an unfavourable prognostic value in high-grade gliomas and may contribute to a pro-tumourigenic microenvironment.
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