Immune signature in the microenvironment of SOLID tumors
The complex interaction between tumor cells and the immune system is described in the concept of cancer immunoediting, which is composed of three phases: the elimination phase, in which innate and adaptive immune cells destroy developing tumors before they become clinically detectable; the equilibrium phase, in which tumor cells that develop resistance to effector immune cells survive but stay dormant under the pressure of immune mechanisms; the escape phase occurring when this equilibrium is lost because tumors acquire new properties that circumvent immune recognition and destruction. Our projects aim to investigate the role played by specific innate and adaptive cell populations in this complex interaction, by providing a deep transcriptomic, phenotypic and functional immune characterization in different types of human solid cancers. The results of these studies are expected to provide new insights into the comprehension of anti-tumor immune mechanisms, and to identify novel cellular and molecular targets to be used in patient follow-up and cancer immunotherapy.
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This project aims to elucidate the evolving mechanisms of the immune response in early and advanced stages of gynecological malignances, crucial for understanding tumor progression and developing effective therapeutic treatments.
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Thymic epithelial tumors are characterized by a strong association with autoimmune diseases that represents a clinical challenge affecting the quality of life and the therapeutic options for the patients. In this project we are investigating the cellular and molecular mechanisms underlying this association, to improve the clinical monitoring and treatment of these patients.
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This project aims to unveil mechanisms of tumor immune evasion in both primary liver and metastasis liver tumors, identifying novel prognostic and predictive biomarkers for tumor progression, recurrence, and therapeutic treatments.
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The project aims to study the interplay between immune response, microbial colonization and surface textures in the pathogenesis of breast implant-associated Anaplastic large cells lymphoma (BIA-ALCL).
Innate lymphiod cells in hematologic malignancies
Innate lymphoid cells (ILCs) are the innate counterparts of T cells, mirroring helper (ILC1, 2, 3) and cytotoxic (NK cells) T cell function. ILCs are emerging as important actors in the pathophysiology of both solid and hematologic cancers by generating a suppressive and tolerant environment. We thus aim at performing a comprehensive immune-phenotypic and functional characterization of ILCs to understand their role in determining the prognosis of hematologic malignancies as well as the responses of patients to the current available therapeutic strategies, including hematopoietic stem cell transplantation. The results that we will obtain will have a clinical utility to identify new clinically relevant prognostic variables and predictive factors of therapy response and to optimize strategies for post-transplant management.
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This project aims to study the role of unconventional NK cell subsets and other ILC in human NK cell ontogenesis to expand the knowledge of this physiological process and to understand its perturbation favoring the pathogenesis of Myelodysplastic syndromes.
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The aim of this project is to investigate the role of innate lymphocytes in the pathogenesis and prognosis of myelodysplastic syndromes to improve the management of patients in terms of prognostic risk assessment and choice of best therapeutic strategy.
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Haploidentical hematopoietic stem cell transplantation is a curative option for hematologic malignancies. The comprehension of immune-reconstitution kinetic and quality could predict opportunistic infections and Graft versus Host Disease, improving the clearance of tumor cells.
endothelial dysfunction
The study of endothelial dysfunction (ED) is crucial to identify the pathogenesis of cardiovascular diseases and provide treatment indications but is hindered by the limited availability of patient-specific primary endothelial cells (ECs). Endothelial colony-forming cells (ECFCs) – EC progenitors involved in EC homeostasis - represent a non-invasive tool to overcome this issue. Thanks to our long-standing experience in ECFC characterization and by applying in vitro assays that evaluate the ECFC ability to promote thrombosis, we are now studying ED in unprovoked venous thromboembolism (uVTE) and anti-phospholipid syndrome (APS). Combining EC-based assays with extracellular vesicle characterization, we are also studying ED in patients receiving CART-cell therapy for lymphoproliferative diseases.
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This study investigates the role of endothelial dysfunction in the pathogenesis of unprovoked venous thromboembolism (uVTE) and in VTE recurrence through the characterization of patient-derived endothelial colony-forming cells (ECFCs).
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In this project, patient-derived endothelial colony-forming cells (ECFCs) are used to investigate alterations of the endothelial compartment in order to disclose the role and the mechanism(s) of endothelial dysfunction in antiphospholipid syndrome.
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CAR-T cells are a promising immunotherapeutic option in relapsed/refractory lymphoproliferative diseases but are associated with significant toxicity characterized by endothelial activation and dysfunction. This project aims at investigating the role of extracellular vesicles in this context.
Innate immunity in SARS-CoV-2 infection and vaccination
The disease progression of SARS-CoV-2 infection can be either asymptomatic or develop into life-threatening pneumonia. The reasons for this dichotomy are still unknown but are partly due to the profile of the patient’s immune response, therefore a better understanding of its magnitude, specificity and kinetics is crucial to the treatment of Covid-19 patients. For these reasons, we are studying the impact of both SARS-CoV-2 infection, in the acute phase and its neurological and neuropsychological complications (NeuroCOVID), and upon vaccination on the homeostasis of immune cells naturally endowed with the highest antiviral activities: NK cells, unconventional T cells (γδ T cells and MAIT cells) and DCs.
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The European consortium NeuroCOV investigates the neurological and neuropsychological complications due to COVID-19 (NeuroCOVID) in order to identify risk factors, develop strategies of monitoring/treatment, and addressing its societal consequences.
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This project aims to investigate the effects of SARS-CoV-2 infection during the acute phase as well as the impact of vaccination on the homeostasis of innate immune cells including NK cells, unconventional T cells (MAIT cells and γδ T cells), and DCs.
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This project aims at evaluating the role of distinct molecular components of prototypic RNA-based vaccines in the induction of an immune-mediated response and identifying biomarkers that predict the optimal balance between protective and not-harmful immune activation.
COMPLETED PRoJECTS
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Diffuse glioma is an aggressive brain cancer characterized by poor prognosis and a highly immunosuppressive tumor microenvironment. A better understanding of the role played by different glioma-infiltrating immune cell populations is needed to improve immunotherapeutic strategies in these patients.
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Primary biliary cholangitis (PBC) is a liver disease characterized by the destruction of intra-hepatic bile ducts. In this project, we aim to investigate the pathogenic role of NK cells and to characterize the mechanisms of NK-mediated epithelial cell destruction in PBC.