Biology subjects

Aubry, I.

Publications and source records attributed to Aubry, I..

3 recordsLinked to original sources

bioRxiv2025

The PTPN1 and PTPN2 phosphatases are Cooperative Regulators of Cancer Cell Immune Evasion

Immune evasion by cancer cells remains a major barrier to the success of immune checkpoint blockade (ICB). Here, we identify the phosphatases PTPN1 and PTPN2 as cooperative regulators of tumor immune resistance. Dual genetic ablation of PTPN1/2 in cancer cells enhances Type I and II interferon signaling, MHC-I and CXCL9 expression, and sensitizes tumor cells to cytotoxic T lymphocyte-mediated killing. The small-molecule inhibitor KQ791 phenocopies these effects and synergizes with anti-PD1 therapy to suppress tumor growth in murine models, including immunotherapy-refractory cancers. Mechanistically, PTPN1/2 loss augments STAT1/3/5 signaling and primes cancer cells for immunogenic cell death via IFN{gamma}/TNF-induced pathways. Moreover, PTPN1/2 inhibition enhances antigen release and cross-presentation, promoting robust antigen-specific CD8 T cell responses. These findings highlight PTPN1&2 as essential mediators of cancer immune evasion and support their inhibition as a strategy to broaden the effectiveness of immune checkpoint blockade in solid tumors.

cancer biology↗

bioRxiv2024

PTPRS is a novel marker for early tau pathology and synaptic integrity in Alzheimer's disease

We examined the role of protein tyrosine phosphatase receptor sigma (PTPRS) in the context of Alzheimers disease and synaptic integrity. Publicly available datasets (BRAINEAC, ROSMAP, ADC1) and a cohort of asymptomatic but "at risk" individuals (PREVENT-AD) were used to explore the relationship between PTPRS and various Alzheimers disease biomarkers. We identified that PTPRS rs10415488 variant C shows features of neuroprotection against early tau pathology and synaptic degeneration in Alzheimers disease. This single nucleotide polymorphism correlated with higher PTPRS transcript abundance and lower P-tau181 and GAP-43 levels in the CSF. In the brain, PTPRS protein abundance was significantly correlated with the quantity of two markers of synaptic integrity: SNAP25 and SYT-1. We also found the presence of sexual dimorphism for PTPRS, with higher CSF concentrations in males than females. Male carriers for variant C were found to have a 10-month delay in the onset of AD. We thus conclude that PTPRS acts as a neuroprotective receptor in Alzheimers disease. Its protective effect is most important in males, in whom it postpones the age of onset of the disease.

neuroscience↗

bioRxiv2021

Brief exposure of neuronal cells to levels of short chain fatty acids observed in human systemic circulation impair the cell lipid metabolism resulting in associated cell death by apoptosis

Communication between gut microbiota and the brain is an enigma. Alterations in the gut microbial community affects enteric metabolite levels, such as SCFAs. SCFAs have been proposed as a possible mechanism through which the gut microbiome modulate brain health and function. This study analyzed for the first time the effects of SCFAs at levels reported in human systemic circulation on human neuronal cell energy metabolism, viability, survival and the brain lipidome. Cell and rat brain lipidomics was done using UHPLC-HESI-HRAMS/MS. Neuronal cells viability, survival and energy metabolism were analyzed via flow cytometer, immunofluorescence, and SeahorseXF platform. Lipidomics analysis demonstrated that SCFAs significantly remodeled the brain lipidome in vivo and in vitro. The most notable remodulation was observed in the metabolism of phosphatidylethanolamine plasmalogens, and mitochondrial lipids carnitine and cardiolipin. Increased mitochondrial mass, fragmentation, and hyperfusion occurred concomitant with the altered mitochondrial lipid metabolism resulting in decreased neuronal cell respiration, ATP production, and increased cell death. This suggests SCFAs at levels observed in human systemic circulation can adversely alter the brain lipidome and neuronal cell function potentially negatively impacting brain health outcomes.

neuroscience↗