Biology subjects

Czabanka, M.

Publications and source records attributed to Czabanka, M..

3 recordsLinked to original sources

bioRxiv2025

Decoding the immune response in leptomeningeal disease through single-cell sequencing of cerebrospinal fluid

AbstractAssessing anti-tumor immune responses and immune microenvironments in central nervous system (CNS) neoplasms, such as brain tumors and leptomeningeal disease (LMD), provides prognostic insights and predictive biomarkers. Liquid biopsy of the cerebrospinal fluid (CSF) represents a promising minimally-invasive approach, but its ability to reflect immune responses against tumors remains unclear. Here, we used single-cell sequencing of CSF cells and spatial transcriptomics of CNS lesions to compare and contrast LMD patients with CNS lymphoma (CNSL), glioblastoma (GB) and brain metastases (BrM), to neuroinflammatory CNS disorders. We identified disease-specific CSF environments, reflecting parenchymal tumor microenvironment features. CNSL showed robust T cell responses, while BrM and GB were dominated by both blood-derived and tissue-resident myeloid cells. Longitudinal CSF sampling unveiled mechanisms of disease progression and therapy resistance, highlighting the potential of CSF liquid biopsies for uncovering disease biology, discovering cellular biomarkers and developing personalized therapies for CNS neoplasms.

immunology↗

bioRxiv2024

Modulation of the ATP-adenosine signaling axis combined with radiotherapy facilitates anti-cancer immunity in brain metastasis

The immunosuppressive microenvironment in the brain poses a major limitation to successful therapy for brain metastases. Here we report that blockade of the ATP-to-adenosine-converting enzymes CD39 and CD73 and the adenosine receptor A2AR in combination with radiotherapy attenuates tumor progression in a breast-to-brain metastasis model by facilitating anti-cancer immunity. Immunophenotyping revealed loss of exhausted T cells and higher abundance of anti-cancer effector T cell populations. This effect was accompanied by a decrease of immunosuppressive lipid-laden macrophages and an expansion of CD14CD33high macrophages associated with antigen presentation. Analyses of human brain metastases samples supports a role of the ATP-adenosine signaling axis in modulating tumor inflammation and identified expression of CD39 and adenosine deaminase as predictive markers for patient survival and/or immune infiltration. Our findings demonstrate that the adenosine axis represents a druggable pathway to achieve local immunomodulation and treatment response, opening a new therapeutic avenue for brain metastases patients.

cancer biology↗

bioRxiv2017

Targeting xCT-Mediated Glutamate Release Normalizes Tumor Angiogenesis In The Brain

Brain tumors are among the most malignant primary tumors, hallmarked by angiogenesis, neuronal destruction and brain swelling. Inhibition of the glutamate-cystein antiporter xCT (system xc-/SLC7A11) alleviates seizures, neuronal cell death and tumor-associated brain edema. Here we show enhanced tumor vessel growth and increased brain edema in xCT-expressing brain tumors. Furthermore, xCT-mediated glutamate impacts directly on endothelial cells in an N-methyl-D-aspartate receptor (NMDAR) dependent manner with intracellular Ca2+ release. Cerebral intravital microscopy revealed that xCT-driven tumor vessels are functional and display increased permeability. Endothelial-cell-specific NMDAR1 knockout mice (GRINi{Delta}EC) show suppressed endothelial sprouting and vascular density compared to control littermates. In addition, implanted gliomas in GRINi{Delta}EC mice display reduced tumor vessels in contrast to gliomas in wildtype animals. Moreover, therapeutic targeting of xCT in gliomas alleviates tumor angiogenesis to normalized levels comparable to controls. Our data reveal that xCT and its substrate glutamate specifically operate on endothelial cells and promote neoangiogenesis. Thus, targeting xCT expression and glutamate secretion in gliomas provides a novel therapeutic roadmap for normalizing tumor angiogenesis.

cell biology↗