Tumour necrosis factor receptor superfamily member 9 (<scp>TNFRSF</scp>9) is up‐regulated in reactive astrocytes in human gliomas

Blank, Anna-Eva; Baumgarten, Peter; Zeiner, Pia S.; Zachskorn, Cornelia; Löffler, Christian; Schittenhelm, Jens; Czupalla, Cathrin J.; Capper, David; Plate, Karl H.; Harter, Patrick N.; Mittelbronn, Michel

doi:10.1111/nan.12135

Cited by 6 publications

(6 citation statements)

References 35 publications

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“…8b). Confusion matrix analysis of CSF analytes revealed high predictive power of a pattern composed of TRAIL, IFN-γ and TNFRSF9 12,44,[47][48][49] (Fig. 8b).…”

Section: Lower Gmvs In Olfactory Pathway Structures In Neuro-covid Pa...mentioning

confidence: 97%

Severe Neuro-COVID is associated with peripheral immune signatures, autoimmunity and neurodegeneration: a prospective cross-sectional study

et al. 2022

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Growing evidence links COVID-19 with acute and long-term neurological dysfunction. However, the pathophysiological mechanisms resulting in central nervous system involvement remain unclear, posing both diagnostic and therapeutic challenges. Here we show outcomes of a cross-sectional clinical study (NCT04472013) including clinical and imaging data and corresponding multidimensional characterization of immune mediators in the cerebrospinal fluid (CSF) and plasma of patients belonging to different Neuro-COVID severity classes. The most prominent signs of severe Neuro-COVID are blood-brain barrier (BBB) impairment, elevated microglia activation markers and a polyclonal B cell response targeting self-antigens and non-self-antigens. COVID-19 patients show decreased regional brain volumes associating with specific CSF parameters, however, COVID-19 patients characterized by plasma cytokine storm are presenting with a non-inflammatory CSF profile. Post-acute COVID-19 syndrome strongly associates with a distinctive set of CSF and plasma mediators. Collectively, we identify several potentially actionable targets to prevent or intervene with the neurological consequences of SARS-CoV-2 infection.

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“…8b). Confusion matrix analysis of CSF analytes revealed high predictive power of a pattern composed of TRAIL, IFN-γ and TNFRSF9 12,44,[47][48][49] (Fig. 8b).…”

Section: Lower Gmvs In Olfactory Pathway Structures In Neuro-covid Pa...mentioning

confidence: 97%

Severe Neuro-COVID is associated with peripheral immune signatures, autoimmunity and neurodegeneration: a prospective cross-sectional study

et al. 2022

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“…High PTPRC expression in glioma could result in both pro-and anti-immune responses (54). TNFRSF9 is upregulated in human gliomas compared to that in normal brain tissue (55), but its effect on gliomas has not been extensively studied. Further, TNFSF4 has not yet been studied in glioma.…”

Section: Discussionmentioning

confidence: 99%

Tumor microenvironment variation implicates immune alterations and correlates with prognosis in patients with glioma

Chen,

He,

Feng

et al. 2024

Preprint

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To investigate the microenvironment composition of gliomas and the associated clinical significance, we analyzed single-cell RNA sequencing and bulk RNA-seq data from glioma samples. Cell trajectory analysis identified five trajectories with distinct cell states and corresponding trajectory-related genes (TRGs). TRG-based clustering segregated patients with glioma with different overall survival, clinicopathological features, immune infiltration status, and immune checkpoint gene (ICG) expression levels. Notably, a worse prognosis was seen in patients with a higher immune score, lower tumor purity, higher M0 macrophage and regulatory T (Treg) cell infiltration, and increased ICG expression. Further survival analysis and functional enrichment analysis revealed a close relationship between prognosis and ICG-associated immunosuppressive pathways. Candidate prognostic genes were obtained using WGCNA analysis and differential expression analysis. LASSO and multivariate regression analysis were used to establish a prognostic prediction model. The prognostic risk-scoring signature including 12 genes successfully predicted patient survival with acceptable AUC values. A nomogram was constructed to evaluate the contribution of the risk signature to patient prognosis. This study highlights the potential involvement of tumor microenvironment variation and immune alteration in glioma progression and establishes a TRG-based prognostic model to predict patient clinical outcomes.

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“…[12] Tissue labeling was performed using the Discovery XT immunohistochemistry system (Ventana Medical Systems, France). A cell conditioning pretreatment was performed for 68 min followed by a 4 min blocking step with inhibitor D. The primary antibody was applied for 32 min, followed by secondary antibody (Discovery Universal Secondary Antibody) for 32 min.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…[12] Melanoma cells of brain metastasis showed a very heterogeneous TNFRSF9 staining pattern [ Figure 1b]. Frequently, TNFRSF9 expression on melanoma cells became stronger with increasing distance from intra-tumoral blood vessels [ Figure 1b], especially in perinecrotic areas.…”

Section: Tumor Necrosis Factor Receptor Superfamily Member 9 Is Exprementioning

confidence: 99%

“…[11] In a previous study, our group showed that TNFRSF9 was strongly upregulated by reactive astrocytes (so-called gemistocytes) in primary central nervous system (CNS) tumors, whereas both brain tumor cells and TIL were mainly TNFRSF9-negative. [12] Since most studies have only focused on TNFRSF9 expression on hematopoietic cells, there is an urgent need to decipher TNFRSF9 expression on other cell types and different microenvironmental conditions in vivo in more detail. Of note, a recent animal study discovered that TNFRSF9 is also expressed in neural stem cells, in which it induced cell death.…”

Section: Introductionmentioning

confidence: 99%

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Tumor necrosis factor receptor superfamily member 9 is upregulated in the endothelium and tumor cells in melanoma brain metastasis

Harter¹,

Blank²,

Weide³

et al. 2014

Neuroimmunol Neuroinflammation

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Tumour necrosis factor receptor superfamily member 9 (TNFRSF9) is up‐regulated in reactive astrocytes in human gliomas

Abstract: Our findings provide a novel, TNFRSF9-positive, reactive astrocytic phenotype and challenge the therapeutic suitability of TNFRSF9 as a promising target for human gliomas.

Cited by 6 publications

References 35 publications

Severe Neuro-COVID is associated with peripheral immune signatures, autoimmunity and neurodegeneration: a prospective cross-sectional study

Severe Neuro-COVID is associated with peripheral immune signatures, autoimmunity and neurodegeneration: a prospective cross-sectional study

Tumor microenvironment variation implicates immune alterations and correlates with prognosis in patients with glioma

Tumor necrosis factor receptor superfamily member 9 is upregulated in the endothelium and tumor cells in melanoma brain metastasis

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