A5041554052- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- Extracellular vesicles in disease
- MicroRNA in disease regulation
- Immune Cell Function and Interaction
- Nanoplatforms for cancer theranostics
- Phagocytosis and Immune Regulation
- Cancer Research and Treatments
- Acute Myeloid Leukemia Research
- Cancer-related gene regulation
- Acute Lymphoblastic Leukemia research
- Wnt/β-catenin signaling in development and cancer
- Mesenchymal stem cell research
- CAR-T cell therapy research
- Neuroendocrine Tumor Research Advances
- Genomics, phytochemicals, and oxidative stress
- Immunotherapy and Immune Responses
- Neonatal Respiratory Health Research
- Chronic Myeloid Leukemia Treatments
- RNA Interference and Gene Delivery
- Histone Deacetylase Inhibitors Research
- Kruppel-like factors research
- Lung Cancer Treatments and Mutations
- Cell Adhesion Molecules Research
- Tuberculosis Research and Epidemiology
University of Verona
2016-2024
Istituto Giannina Gaslini
2017-2021
Istituti di Ricovero e Cura a Carattere Scientifico
2021
Washington Center
2018
University of Washington
2018
Abstract Mesenchymal stromal cells (MSCs) are multipotent cells, immunomodulatory stem that currently used for regenerative medicine and treatment of a number inflammatory diseases, thanks to their ability significantly influence tissue microenvironments through the secretion large variety soluble factors. Recently, several groups have reported presence extracellular vesicles (EVs) within MSC secretoma, showing beneficial effect in different animal models disease. Here, we standardized...
Myeloid cells can restrain antitumor immunity by metabolic pathways, such as the degradation of l-arginine, whose concentrations are regulated arginase 1 (ARG1) enzyme. Results from preclinical studies indicate important role arginine metabolism in pancreatic ductal adenocarcinoma (PDAC) progression, suggesting a potential for clinical application; however, divergent evolution ARG1 expression and function rodents humans has restricted translation. To overcome this dichotomy, here, we show...
Mesenchymal stromal cells (MSCs) are adult, multipotent of mesodermal origin representing the progenitors all tissues. MSCs possess significant and broad immunomodulatory functions affecting both adaptive innate immune responses once primed by inflammatory microenvironment. Recently, role extracellular vesicles (EVs) in mediating therapeutic effects has been recognized. Nevertheless, molecular mechanisms responsible for properties MSC-derived EVs (MSC-EVs) still poorly characterized....
Expression of the L-arginine catabolizing enzyme arginase 1 (ARG1) is a central immunosuppressive mechanism mediated by tumor-educated myeloid cells. Increased activity ARG1 promotes formation an microenvironment and leads to more aggressive phenotype in many cancers. Intrinsic T-cell immunity against ARG1-derived epitopes peripheral blood cancer patients healthy subjects has previously been demonstrated. To evaluate antitumor efficacy peptide vaccines as monotherapy combinational therapy...
In this study, a successful medicinal chemistry campaign that exploited virtual, biophysical, and biological investigations led to the identification of novel class IDO1 inhibitors based on benzimidazole substructure. This family compounds is endowed with an extensive bonding network in protein active site, including interaction pocket C, region not commonly by previously reported inhibitors. The tight packing selected within enzyme contributes strong binding IDO1, inhibitory potency at low...
Abstract Graft-vs-host-disease (GvHD) is currently the main complication of allogeneic hematopoietic stem cell transplantation. Mortality and morbidity rates are particularly high, especially in steroid-refractory acute GvHD (aGvHD). Immune regulatory human bone marrow mesenchymal stromal cells (hMB-MSCs) represent a therapeutic approach to address this issue. Unfortunately, their effect hardly predictable vivo due several variables, that is, MSC tissue origin, concentration, dose number,...
The dysregulation of the axon guidance pathway is common in pancreatic ductal adenocarcinoma (PDAC), yet our understanding its biological relevance limited. Here, we investigated functional role cue SEMA3A supporting PDAC progression.
In this study, we compared the overall gene and pathway expression profiles of HS-5 HS-27A stromal cell lines with those primary bone marrow MSCs to verify if they can be considered a reliable alternative tool for evaluating contribution in tumor development immunomodulation. Indeed, due their easier manipulation vitro as MSC cultures, several published studies took advantage assess biological mechanisms mediated by cells influencing biology immune responses. However, process carried out...
Heterozygous mutations in the PHOX2B gene are causative of congenital central hypoventilation syndrome (CCHS), a neurocristopathy characterized by defective autonomic control breathing due to impaired differentiation neural crest cells. Among mutations, polyalanine (polyAla) expansions almost exclusively associated with isolated CCHS, whereas frameshift variants, although less frequent, often more severe than polyAla and identified syndromic CCHS. This article provides complete review all...
Abstract Notch3 and Notch4 support survival of primary B-cell acute lymphoblastic leukemia (B-ALL) cells, suggesting a role for Notch signaling in drug response. Here we used vitro, silico, vivo mouse xenograft model-based approaches to define the pathway B-ALL chemosensitivity. We observed significant receptor ligand expression cells cell lines. Primary from high-risk patients overexpressed Notch3, Notch4, Jagged2 while displaying reduction levels Notch1-4 following chemotherapy. then...
Cancer cells favor the generation of myeloid with immunosuppressive and inflammatory features, including myeloid-derived suppressor (MDSCs), which support tumor progression. The anti-apoptotic molecule, cellular FLICE (FADD-like interleukin-1β-converting enzyme)-inhibitory protein (c-FLIP), acts as an important modulator caspase-8, is required for development function monocytic (M)-MDSCs. Here, we assessed effect immune checkpoint inhibitor (ICI) therapy on systemic immunological landscape,...
Abstract Inflammatory responses rapidly detect pathogen invasion and mount a regulated reaction. However, dysregulated anti-pathogen immune can provoke life-threatening inflammatory pathologies collectively known as cytokine release syndrome (CRS), exemplified by key clinical phenotypes unearthed during the SARS-CoV-2 pandemic. The underlying pathophysiology of CRS remains elusive. We found that FLIP, protein controls caspase-8 death pathways, was highly expressed in myeloid cells COVID-19...
Wnt/β-catenin signaling has been reported in Acute Myeloid leukemia, but little is known about its significance as a prognostic biomarker and drug target. In this study, we first evaluated the correlation between expression levels of Wnt molecules clinical outcome. Then, studied—in vitro vivo—the anti-leukemic value combinatorial treatment inhibitors classic anti-leukemia drugs. Higher β-catenin, Ser675-phospho-β-catenin GSK-3α (total Ser 9) were found AML cells from intermediate or poor...
Abstract Motivation Cytometry comprises powerful techniques for analyzing the cell heterogeneity of a biological sample by examining expression protein markers. These technologies impact especially field oncoimmunology, where identification is essential to analyze tumor microenvironment. Several classification tools have been developed annotation cytometry datasets, which include supervised that require training set as reference (i.e. reference-based) and semisupervised based on manual...
Indoleamine 2,3-dioxygenase 1 (IDO1) plays a key role in tumor immune escape. Besides being metabolic enzyme that catalyzes the first step of tryptophan catabolism, it also acts as signal-transducing protein, whose partnering with tyrosine phosphatase Src homology 2 (SH2) domain-containing protein substrate (SHPs) and phosphatidylinositol-3-kinase (PI3K) regulatory subunit p85 promotes establishment sustained immunosuppressive phenotype. While IDO1 inhibitors typically interfere its...
In the late B cell differentiation stages, miRNAs expression modifications promoting or inhibiting key pathways are only partially defined. We isolated 29 CD19+ human samples at different stages of differentiation: cells from peripheral blood; naïve, germinal center (GC) and subepithelial (SE) tonsils. SE were further split in activated resting cell. The miRNA profile these was assessed by microarray analysis selected validated quantitative RT-PCR situ hybridization on normal comparison all...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with few available therapeutic options. Two transcriptional cancer cell states have been consistently reported in PDAC, the basal-like/squamous phenotype displaying more aggressive biological behavior. Genetic and epigenetic dysregulation of axon guidance pathway are common yet our understanding its relevance limited. Here, we investigated functional role cue SEMA3A sustaining progression PDAC. We integrated transcriptomic...
The advent of immune checkpoint inhibitors (ICIs), for instance, programmed cell death 1 (PD-1)/PD-1 ligand (PD-L1) blockers, has greatly improved the outcome patients affected by non-small lung cancer (NSCLC). However, most NSCLC either do not respond to ICI monotherapy or develop resistance it after an initial response. Therefore, identification biomarkers predicting response represents urgent issue. Great efforts are currently dedicated toward identifying blood-based predict responses...