Mapping high-grade glioma immune infiltration to 5-ALA fluorescence levels: TCGA data computation, classical histology, and digital image analysis.

Autor: Lang A; Department of Neurosurgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.; Central Nervous System Unit, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria., Jeron RL; Department of Neurosurgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria., Lontzek B; Department of Neurosurgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria., Kiesel B; Department of Neurosurgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.; Central Nervous System Unit, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria., Mischkulnig M; Department of Neurosurgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.; Central Nervous System Unit, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria., Berghoff AS; Department of Medicine I/Division of Oncology, Medical University of Vienna, Vienna, Austria.; Central Nervous System Unit, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria., Ricken G; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria.; Central Nervous System Unit, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria., Wöhrer A; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria.; Central Nervous System Unit, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria., Rössler K; Department of Neurosurgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.; Central Nervous System Unit, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria., Lötsch-Gojo D; Department of Neurosurgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.; Central Nervous System Unit, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria., Roetzer-Pejrimovsky T; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria.; Central Nervous System Unit, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria., Berger W; Center for Cancer Research, Medical University of Vienna, Vienna, Austria., Hainfellner JA; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria.; Central Nervous System Unit, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria., Höftberger R; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria.; Central Nervous System Unit, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria., Widhalm G; Department of Neurosurgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria. georg.widhalm@meduniwien.ac.at.; Central Nervous System Unit, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. georg.widhalm@meduniwien.ac.at., Erhart F; Department of Neurosurgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.; Central Nervous System Unit, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Jazyk: angličtina
Zdroj: Journal of neuro-oncology [J Neurooncol] 2023 Aug; Vol. 164 (1), pp. 211-220. Date of Electronic Publication: 2023 Aug 06.
DOI: 10.1007/s11060-023-04406-3
Abstrakt: Purpose: Resection of high-grade gliomas has been considerably improved by 5-aminolevulinic acid (5-ALA). However, not all neurobiological properties of 5-ALA are fully understood. Specifically, potential differences in immune infiltration have not been conclusively examined, despite recent reports that immune cells might play a role. Thus, we here provide a systematic mapping of immune infiltration of different 5-ALA fluorescence levels.
Methods: Tumor-associated macrophages (CD68, CD163), cytotoxic T cells (CD8), and regulatory T cells (FoxP3) were quantified via three methods. First, data from The Cancer Genome Atlas (TCGA) of 172 patients was examined for correlations between 5-ALA fluorescence-related mRNA expression signatures and immune markers. Second, as classical histology, 508 stained slides from 39 high-grade glioma patients were analysed semi-quantitatively by two independent reviewers, generating 1016 data points. Third, digital image analysis was performed with automated scanning and algorithm-based cell quantification.
Results: TCGA mRNA data from 172 patients showed a direct, significant correlation between 5-ALA signatures and immune markers (p < 0.001). However, we were not able to confirm this finding in the here studied initial set of 39 patient histologies where we found a comparable immune infiltration in different fluorescence levels. Digital image analysis correlated excellently with standard histology.
Conclusion: With mapping the immune infiltration pattern of different 5-ALA categories, we are adding fundamental basic insights to the field of 5-ALA and glioma biology. The observation that a significant correlation in TCGA data did not fully translate to detectable differences in immune infiltration in first histology data warrants further investigation in larger cohorts.
(© 2023. The Author(s).)
Databáze: MEDLINE
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