- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Cytokine Signaling Pathways and Interactions
- CAR-T cell therapy research
- Advanced Biosensing Techniques and Applications
- Lymphoma Diagnosis and Treatment
- Immune Cell Function and Interaction
- interferon and immune responses
- Cancer Immunotherapy and Biomarkers
- Immune Response and Inflammation
- Protein Degradation and Inhibitors
- Viral-associated cancers and disorders
- Cytomegalovirus and herpesvirus research
- Gene expression and cancer classification
- COVID-19 Clinical Research Studies
- T-cell and B-cell Immunology
- Immune cells in cancer
- Viral Infectious Diseases and Gene Expression in Insects
- Stress Responses and Cortisol
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer-related molecular mechanisms research
- Herpesvirus Infections and Treatments
- RNA modifications and cancer
- Virus-based gene therapy research
- SARS-CoV-2 and COVID-19 Research
Istituto Superiore di Sanità
2013-2024
National Institutes of Health Clinical Center
2005-2007
Cancer stem cells (CSCs) are a subpopulation of cancer endowed with high tumorigenic, chemoresistant and metastatic potential. Nongenetic mechanisms acquired resistance increasingly being discovered, but molecular insights into the evolutionary process CSCs limited. Here, we show that type I interferons (IFNs-I) function as hubs during immunogenic chemotherapy, triggering epigenetic regulator demethylase 1B (KDM1B) to promote an adaptive, yet reversible, transcriptional rewiring towards...
Abstract Background Recent studies of cortical pathology in secondary progressive multiple sclerosis have shown that a more severe clinical course and the presence extended subpial grey matter lesions with significant neuronal/glial loss microglial activation are associated meningeal inflammation, including lymphoid-like structures subarachnoid space proportion cases. Methods To investigate molecular consequences pro-inflammatory cytotoxic molecules diffusing from meninges into underlying...
The first report on the antitumor effects of interferon α/β (IFN-I) in mice was published 50 years ago. IFN-α were immunotherapeutic drugs approved by FDA for clinical use cancer. However, their occurred at a time when most mechanisms action still unknown. These cytokines being used as either conventional cytostatic or non-specific biological response modifiers. Specific activities subsequently ascribed to IFN-I poorly considered use. Notably, lot data humans and underlines importance...
Imiquimod is a Toll-like receptor-7 agonist capable of inducing complete clearance basal cell carcinoma (BCC) and other cutaneous malignancies. We hypothesized that the characterization early transcriptional events induced by imiquimod may provide insights about immunological preceding acute tissue and/or tumor rejection. report paired analysis adjacent punch biopsies obtained pre- post-treatment from 36 patients with BCC subjected to local application (n = 22) or vehicle cream 14) in...
Abstract Combination of chemotherapy with cancer vaccines is currently regarded as a potentially valuable therapeutic approach for the treatment some metastatic tumors, but optimal modalities remain unknown. We designed phase I/II pilot study evaluating effects dacarbazine (DTIC) on immune response in HLA‐A2 + disease‐free melanoma patients who received anticancer vaccination 1 day following (800 mg/mq i.v.). The vaccine, consisting combination restricted antigen A (Melan‐A/MART‐1) and gp100...
Certain chemotherapeutic drugs, such as cyclophosphamide (CTX), can enhance the antitumor efficacy of immunotherapy because their capacity to modulate innate and adaptive immunity. Indeed, it has been argued that this may be more significant in general than is currently appreciated. To gain insights into core mechanisms chemoimmunotherapy, we methodically profiled effects CTX on gene expression bone marrow, spleen, peripheral blood, cytokine plasma marrow tumor-bearing mice. Gene protein...
Abstract Type I interferon (IFN-I) is a class of antiviral immunomodulatory cytokines involved in many stages tumor initiation and progression. IFN-I acts directly on cells to inhibit cell growth indirectly by activating immune mount antitumor responses. To understand the role endogenous spontaneous, oncogene-driven carcinogenesis, we characterized tumors arising HER2/neu transgenic (neuT) mice carrying nonfunctional mutation IFNI receptor (IFNAR1). Such are unresponsive this family...
This study was aimed at evaluating the feasibility, safety, immunologic and clinical responses in patients with follicular lymphoma treated monocyte-derived dendritic cells generated presence of IFNα GM-CSF (IFN-DC) combination low doses rituximab.Firstly, we analyzed vitro vivo properties IFN-DC against lymphoma. Thus, performed a phase I trial 8 refractory relapsed based on sequential intranodal injections low-dose rituximab unloaded report clinical, results enrolled patients.Preclinical...
// Ilaria Sciamanna 1 , Alberto Gualtieri 1,5 Cristina Cossetti Emanuele Felice Osimo Manuela Ferracin 2 Gianfranco Macchia Eleonora Aricò Gianni Prosseda 3 Patrizia Vitullo Tom Misteli 4 and Corrado Spadafora Istituto Superiore di Sanità, Viale Regina Elena 299, Rome, Italy. Laboratory for Technologies of Advanced Therapies (LTTA) Department Morphology, Surgery Experimental Medicine, University Ferrara, Biology Biotechnology "Charles Darwin", Sapienza University, National Cancer Institute,...
Advanced melanoma patients have an extremely poor long term prognosis and are in strong need of new therapies. The recently developed targeted therapies resulted a marked antitumor effect, but most responses partial some degree toxicity remain the major concerns. Dendritic cells play key role activation immune system been typically used as ex vivo antigen-loaded cell drugs for cancer immunotherapy. Another approach consists intratumoral injection unloaded DCs that can exploit uptake wider...
The antitumor effectiveness of cyclophosphamide (CTX) and other chemotherapeutics was shown to rely not only on direct cytotoxicity but also immunogenic tumor cell death systemic immunomodulatory mechanisms, including regulatory T (Treg) depletion, Th1 polarization, type I interferon (IFN) proinflammatory cytokine production. IFN factor (IRF)-1 is a transcriptional regulator IFNs IFN-inducible genes, involved in the control Treg differentiation sterile inflammation. Aim this study explore...
We have recently developed a candidate HIV-1 vaccine model based on Pr55gag Virus-Like Particles (HIV-VLPs), produced in baculovirus expression system and presenting gp120 molecule from an Ugandan isolate of the clade A (HIV-VLPAs). The HIV-VLPAs induce Balb/c mice systemic mucosal neutralizing Antibodies as well cytotoxic T lymphocytes, by intra-peritoneal intra-nasal administration. Moreover, we shown that baculovirus-expressed HIV-VLPs maturation activation monocyte-derived dendritic...
Baculovirus-expressed HIV-1 Pr55gag Virus-Like Particles (HIV-VLPs) induce maturation and activation of monocyte-derived dendritic cells (MDDCs) with a production Th1- Th2-specific cytokines. The analysis genomic transcriptional profile MDDCs, obtained from normal healthy donors activated by HIV-VLPs, show the modulation genes involved in morphological functional changes characterizing MDDCs maturation. Similar data are using peripheral blood mononuclear (PBMCs), without further selection,...
Social isolation is a powerful stressor capable of affecting brain plasticity and function. In the case breast cancer, previous data indicate that stressful experiences may contribute to worse prognosis, activating neuroendocrine metabolism pathways, although mechanisms underlying these effects are still poorly understood. this study, we tested hypothesis chronic stress (IS) boost hypothalamic–pituitary–adrenal (HPA) axis activity, leading changes in hypothalamic expression genes modulating...
Abstract Childhood maltreatment is associated with increased severity of substance use disorder and frequent relapse to drug following abstinence. However, the molecular neurobiological substrates that are engaged during early traumatic events mediate greater risk poorly understood knowledge factors date extremely limited. In this study, we modeled childhood by exposing juvenile mice a threatening social experience (social stressed, S‐S). We showed S‐S influenced propensity reinstate...
Interferon (IFN)-alpha is considered a key modulator of immunopathological processes through signature-specific activation mononuclear phagocytes (MPs). This study utilized global transcript analysis to characterize the effects entire type I IFN family in comparison broad panel other cytokines on MP previously exposed Lipopolysaccharide (LPS) stimulation vitro.Immature peripheral blood CD14+ MPs were stimulated with LPS and 1 hour later 42 separate soluble factors including cytokines,...
Interferons alpha (IFNα) are the cytokines most widely used in clinical medicine for treatment of cancer and viral infections. Among immunomodulatory activities possibly involved their therapeutic efficacy, importance IFNα effects on dendritic cells (DC) differentiation activation has been considered. Despite several studies exploiting microarray technology to characterize mechanisms action, there is currently no consensus core signature these peripheral blood IFNα-treated individuals, as...
Abstract Background Prevention and treatment of metastatic breast cancer (BC) is an unmet clinical need. The retinoic acid derivative fenretinide (FeR) was previously evaluated in Phase I-III trials but, despite its excellent tolerability antitumor activity preclinical models, showed limited therapeutic efficacy due to poor bioavailability. We recently generated a new micellar formulation FeR, Bionanofenretinide (Bio-nFeR) showing enhanced bioavailability, low toxicity, strong on human lung...