Biology subjects

Schmid, A. M.

Publications and source records attributed to Schmid, A. M..

3 recordsLinked to original sources

bioRxiv2026

Immune-metabolic PET/MRI uncovers microenvironmental reprogramming under combined immunotherapy and anti-angiogenic therapy

The limited efficacy of immune checkpoint inhibitor (ICI) therapy in triple-negative breast cancer (TNBC) highlights the need for combination strategies that enhance antitumor responses. Sorafenib, a multikinase inhibitor with anti-angiogenic and immunomodulatory activity, represents a rational partner for ICI-based combination therapy. However, therapeutic responses to such combinations are biologically complex and cannot be fully characterized by any single biomarker or imaging modality. Here, we evaluated ICI therapy combined with sorafenib in the aggressive and ICI-refractory orthotopic 4T1 TNBC model. Therapeutic responses were assessed using a unique longitudinal multimodal imaging framework integrating [Zr]Zr-DFO-anti-CD8 minibody and [{superscript 1}F]FDG PET, as well as perfluorocarbon (PFC)-based {superscript 1}F MRI and hyperpolarized {superscript 1}3C MRS, together with ex vivo analyses. Only the ICI-sorafenib combination suppressed tumor growth, whereas both monotherapies showed limited antitumor activity. Multimodal imaging, together with complementary ex vivo analyses, uncovered coordinated tumor microenvironment (TME) remodeling, including vascular normalization, elevated CD8 cell presence with modest enrichment in the tumor center, delayed increase in phagocyte-associated {superscript 1}F MRI signal coupled with reduced CD206 cell infiltration, and sustained metabolic activity. These findings support ICI-sorafenib combination therapy as a promising therapeutic strategy for TNBC. Therapeutic efficacy reflected coordinated vascular, immune, and metabolic remodeling. This multimodal imaging framework enables non-invasive longitudinal monitoring of these complementary TME changes, providing a comprehensive strategy for treatment assessment in immunotherapy-based combination therapies. One Sentence SummaryLongitudinal multimodal imaging identified a multidimensional TME response signature of effective ICI-sorafenib therapy in TNBC.

cancer biology↗

bioRxiv2025

Extracellular vesicles as indicators of environmental stress response in Lactiplantibacillus plantarum: a multi-platform study

Extracellular vesicles (EVs) are key mediators of bacterial communication and adaptation to environmental stress. Their size, cargo, and surface charge are influenced by several factors, including environmental conditions, bacterial physiology, and isolation methods, and are highly strain-specific. Herein, we investigated how exposure to bile, a physiological component of the gut environment, affects the production and properties of EVs released by the probiotic strain Lactiplantibacillus plantarum NCIMB 8826. Through ultracentrifugation followed by size-exclusion chromatography (SEC), we isolated highly purified L. plantarum EVs (LpEVs) and characterized them according to the Minimal Information for Studies of Extracellular Vesicles guidelines. SEC purification significantly reduced the contents of contaminating proteins and peptidoglycans, improving the compositional purity of the isolated EVs. Compared with the parent bacteria, purified LpEVs exhibited distinct surface lipid profiles and zeta potential as well as remarkable stability across varying pH levels, elevated NaCl concentrations, and increasing detergent challenges. Under bile stress, the bacteria released larger LpEVs enriched in bile metabolism-related proteins, suggesting vesicle-mediated adaptation. Fourier-transform infrared spectroscopy further revealed bile-induced molecular alterations in LpEVs that differed from those in the parent bacteria. These findings highlight bacterial EVs as dynamic environmental communicators that respond to stress and may modulate host-microbe interactions before detectable changes occur in the bacterial cells.

microbiology↗

bioRxiv2023

Western diet increases brain metabolism and adaptive immune responses in a mouse model of amyloidosis

Diet-induced body weight gain is a growing health problem worldwide, leading to several serious systemic diseases such as diabetes. Because it is often accompanied by a low-grade metabolic inflammation that alters systemic function, dietary changes may also contribute to the progression of neurodegenerative diseases. Here we demonstrate disrupted glucose and fatty acid metabolism and a disrupted plasma metabolome in a mouse model of Alzheimers disease following a western diet using a multimodal imaging approach and NMR-based metabolomics. We did not detect glial-dependent neuroinflammation, however using flow cytometry we observed T cell recruitment in the brains of western diet-fed mice. Our study highlights the role of the brain-liver-fat-axis and the adaptive immune system in the disruption of brain homeostasis due to a Western diet.

immunology↗