Publications by authors named "V Marschall"
Article Synopsis
- Reactive oxygen species (ROS) are known for causing cellular damage and cancer, but they also play a crucial role in cellular signaling and maintaining homeostasis, particularly through the action of NADPH oxidase 4 (Nox4).
- Research using mouse models revealed that deleting Nox4 increases tumor formation and reduces the ability to recognize DNA damage, as it disrupts the phosphorylation of γH2AX, a key marker for DNA damage.
- Nox4 maintains low levels of the phosphatase PP2A in the nucleus, which is essential for effective DNA damage surveillance; without it, there's enhanced AKT phosphorylation leading to uncontrolled cell proliferation and genomic instability, both of which contribute to cancer development.
Background: Glucocorticoid-induced TNFR-related protein (TNFRSF18, GITR, CD357), expressed by T cells, and its ligand (TNFSF18, GITRL), expressed by myeloid populations, provide co-stimulatory signals that boost T cell activity. Due to the important role that GITR plays in regulating immune functions, agonistic stimulation of GITR is a promising therapeutic concept. Multiple strategies to induce GITR signaling have been investigated.
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- TNFRSF7 (CD27) and its ligand CD27L (CD70) enhance T cell activation, differentiation, and survival, making them important targets for immuno-oncology therapies aimed at boosting T cell responses against tumors.
- HERA-CD27L is a newly developed xavalent TNF receptor agonist that mimics natural signaling and significantly improves antigen-specific T cell responses while showing effectiveness in tumor models without affecting non-specific T cells.
- The combination of HERA-CD27L with anti-PD-1 antibodies has been shown to have additive anti-tumor effects, emphasizing the synergistic role of T cell activation and checkpoint inhibition in enhancing anti-tumor immunity.
Article Synopsis
- CD40 ligand is crucial for immune regulation and targeting CD40 with new therapies holds promise for cancer treatment.
- Most existing CD40-targeting drugs rely on antibodies, which have limitations like needing crosslinking and causing immune cell depletion.
- The novel HERA Technology, which creates hexavalent receptor agonists like HERA-CD40L, overcomes these issues, leading to stronger immune activation and effective antitumor responses without relying on crosslinking.
Small-molecule inhibitors of Inhibitor of Apoptosis proteins such as Smac mimetics have been reported to provide a promising tool to sensitize glioblastoma (GBM) cells to cytotoxic therapies including chemotherapeutic drugs. However, the underlying molecular mechanisms of action have not yet been fully unraveled. In the present study, we therefore investigated the role of reactive oxygen species (ROS) in the regulation of Smac mimetic/temozolomide (TMZ)-induced cell death in GBM cells.
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