Biology subjects

Quintanilla-Martinez, L.

Publications and source records attributed to Quintanilla-Martinez, L..

4 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↗

bioRxiv2026

Loss of systemic anti-viral immunity and LMP1-driven suppressive myeloid tumour niches converge to shape the immunobiology of EBV+ diffuse large B-cell lymphoma

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (EBVDLBCL) is an aggressive lymphoma with poor outcomes and an incompletely understood pathogenesis, frequently attributed to immunosenescence. However, its occurrence across all age groups suggests alternative mechanisms. Here, we integrate functional profiling of peripheral antiviral T-cell immunity with high-dimensional spatial proteomics and mechanistic in vitro modelling to define the immunological landscape of EBVDLBCL. We show that both EBV and EBV-DLBCL patients exhibit broad impairments in antiviral T-cell responses compared with healthy controls, affecting latent and lytic EBV antigens as well as non-EBV viral targets, with deficits most pronounced in EBV patients. Spatial proteomic analysis revealed that EBVDLBCL harbours a profoundly immunosuppressive tumour microenvironment characterised by relative loss of intratumoural CD8 T cells, expansion of PD-1 regulatory and exhausted T-cell populations, and dense aggregates of PD-L1/IDO1 macrophages. Compared with EBV classical Hodgkin lymphoma and infectious mononucleosis, EBV DLBCL displayed the most marked macrophage-associated immunosuppressive signature and the lowest T-cell density. Suppressive myeloid niches were preferentially enriched around LMP1-expressing tumour cells, a feature not observed in the other EBV-associated conditions. Together, these findings indicate that EBVDLBCL is driven by the convergence of systemic antiviral immune dysfunction and an LMP1-dependent suppressive tumour microenvironment.

cancer biology↗

bioRxiv2023

Active Suppression of the Nigrostriatal Pathway during Optogenetic Stimulation Revealed by Simultaneous fPET/fMRI

The dopaminergic system is a central component of the brains neurobiological framework, governing motor control, reward responses, and playing an essential role in various brain disorders such as Parkinsons disease and schizophrenia. Within this complex network, the nigrostriatal pathway represents a critical circuit for dopamine transmission from the substantia nigra to the striatum, a connection that is vital to understanding many of the disease-related dysfunctions. However, stand-alone functional magnetic resonance imaging (fMRI) is unable to study the intricate interplay between brain activation and its molecular underpinnings. In our study, the simultaneous use of [18F]FDG functional positron emission tomography (fPET)/BOLD-fMRI provided a new insight that allowed us to demonstrate an active suppression of the nigrostriatal activity during optogenetic stimulation via presynaptic autoinhibition. Our in vivo observation emphasizes that the observed BOLD signal depression during neuronal stimulation does not correlate with neuronal inactivity, but results from an active suppression of neuronal firing as shown by the high [18F]FDG signal increase. This result not only illustrates the potential of simultaneous fPET/fMRI to understand the molecular mechanisms of brain function but also provides a new perspective on how neurotransmitters such as dopamine influence hemodynamic responses in the brain.

neuroscience↗

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↗