Biology subjects

Tagliabue, E.

Publications and source records attributed to Tagliabue, E..

3 recordsLinked to original sources

bioRxiv2025

Membrane Sensing Peptides -Enhanced SiMoA Platform for the Detection of HER2 on Extracellular Vesicles in Metastatic Breast Cancer Patients

Extracellular vesicles (EVs) offer a promising avenue for non-invasive, real-time monitoring of metastatic breast cancer (mBC), but clinical application as a liquid biopsy is hindered by their heterogeneity and low abundance. Here we present a Single Molecule Array (SiMoA) platform enhanced by membrane sensing peptides (MSP) for the highly sensitive detection of HER2 on EV membranes (EVs-HER2) and general EVs population (CD9+) directly from plasma samples of mBC patients. The MSP-based SiMoA assay demonstrated superior sensitivity and specificity compared to conventional antibody-based assays, allowing the detection of lower amounts of EVs and discriminating EVs derived from breast cancer patient-derived organoids (BC-PDO) from healthy control-derived organoids (HC-PDO). Concerning the analysis of EVs in plasma samples (n=49 mBC patients, n=30 healthy controls), we observed significantly lower CD9+ EVs levels in mBC patients relative to healthy controls, a trend consistently confirmed across assays. Notably, EVs-HER2 levels were significantly enriched in HER2-positive patients and correlated with clinical HER2 status assessed by immunohistochemistry. Besides, lower CD9+ EVs levels were associated with poorer clinical outcomes, highlighting the potential prognostic utility of EV quantification. Our findings underscore the potential of MSP-enhanced SiMoA platforms for accurate, minimally invasive monitoring of EVs-HER2 in mBC and for monitoring CD9+ EVs levels to assess disease progression.

biochemistry↗

bioRxiv2021

Severity of SARS-CoV-2 infection as a function of the interferon landscape across the respiratory tract of COVID-19 patients.

The COVID-19 outbreak driven by SARS-CoV-2 has caused more than 2.5 million deaths globally, with the most severe cases characterized by over-exuberant production of immune-mediators, the nature of which is not fully understood. Interferons of the type I (IFN-I) or type III (IFN-III) families are potent antivirals, but their role in COVID-19 remains debated. Our analysis of gene and protein expression along the respiratory tract shows that IFNs, especially IFN-III, are over-represented in the lower airways of patients with severe COVID-19, while high levels of IFN-III, and to a lesser extent IFN-I, characterize the upper airways of patients with high viral burden but reduced disease risk or severity; also, IFN expression varies with abundance of the cell types that produce them. Our data point to a dynamic process of inter- and intra-family production of IFNs in COVID-19, and suggest that IFNs play opposing roles at distinct anatomical sites.

immunology↗

bioRxiv2020

Antibiotic-induced disturbances of the gut microbiota result in accelerated breast tumour growth via a mast cell-dependent pathway

The diverse community of commensal microbes that comprise the gut microbiota is known to play an integral role in human health, not least through its ability to regulate host immune responses and metabolic pathways. Alterations to the homeostasis of this community, including through the use of broad-spectrum antibiotics, have already been associated with the progression of several cancers, namely melanoma and liver. The aggressive nature of breast cancer (BrCa), largely due to its ability to metastasize early, has ranked the disease with the second highest mortality rate of all cancers globally. Yet the body of research into the complex relationship between the microbiota and BrCa is still limited. This study found that a depletion of the microbiota, through the administration of antibiotics, significantly increased the rate of primary tumour progression in mouse BrCa models. We show that antibiotic-induced microbiota disturbances lead to changes in behaviour of a relatively obscure tumour-immune cell population: mast cells. We observed increases in tumour stroma-associated mast cells in antibiotic treated animals. Moreover, inhibition of mast cell degranulation, via cromolyn, slowed tumour progression in antibiotic treated animals but not in control animals. Thus, it appears that a perturbed microbiota drives stroma-associated mast cell recruitment and activation, which in turn promotes primary tumour growth through an as yet unknown mechanism. One Sentence Summary: We show that breast cancer progression is accelerated through a unique/novel immune response involving mast cells as a result of an antibiotic induced perturbation of the gut microbiota in a mouse model.

cancer biology↗