A5076278835- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Organometallic Complex Synthesis and Catalysis
- T-cell and B-cell Immunology
- Galectins and Cancer Biology
- Immune cells in cancer
- Immune Response and Inflammation
- Cell Adhesion Molecules Research
- interferon and immune responses
- Chemokine receptors and signaling
- Catalytic Alkyne Reactions
- Monoclonal and Polyclonal Antibodies Research
- Carbon dioxide utilization in catalysis
- Synthetic Organic Chemistry Methods
- CAR-T cell therapy research
- Inorganic and Organometallic Chemistry
- Chemical Synthesis and Reactions
- Phagocytosis and Immune Regulation
- Catalysis and Oxidation Reactions
- Radical Photochemical Reactions
- Catalytic Processes in Materials Science
- Adipose Tissue and Metabolism
- Conducting polymers and applications
- RNA Interference and Gene Delivery
International Centre for Genetic Engineering and Biotechnology
2016-2025
Università di Camerino
2020-2025
University of Florence
2021-2024
Louisiana State University Health Sciences Center New Orleans
2023
Azienda Ospedaliero-Universitaria Careggi
2017-2023
International Centre for Genetic Engineering and Biotechnology
2022
Vitenparken
2014
Solvay (Belgium)
2006-2007
Inserm
2002-2005
Institut Curie
2002-2005
Immune cells experience large cell shape changes during environmental patrolling because of the physical constraints that they encounter while migrating through tissues. These can adapt to such deformation events using dedicated shape-sensing pathways. However, how sensing affects immune function is mostly unknown. Here, we identify a mechanism increases expression chemokine receptor CCR7 and guides dendritic migration from peripheral tissues lymph nodes at steady state. This relies on lipid...
Upon maturation, dendritic cells (DCs) acquire the unique ability to activate naïve T cells. We used time-lapse video microscopy and two-photon imaging of intact lymph nodes show that after establishing initial contact between their dendrites lymphocytes, mature DCs migrate toward contacted lymphocytes. Subsequently, tightly entrap within a complex net membrane extensions. The Rho family guanosine triphosphatases Rac1 Rac2 but not itself control formation in DCs, polarized short-range...
Abstract Mammary epithelial stem cells are fundamental to maintain tissue integrity. Cancer (CSCs) implicated in both treatment resistance and disease relapse, the molecular bases of their malignant properties still poorly understood. Here we show that normal CSCs breast controlled by prolyl‐isomerase Pin1. Mechanistically, following interaction with Pin1, Notch1 Notch4, key regulators cell fate, escape from proteasomal degradation major ubiquitin‐ligase Fbxw7α. Functionally, Fbxw7α acts as...
Abstract The prolyl isomerase PIN1, a critical modifier of multiple signalling pathways, is overexpressed in the majority cancers and its activity strongly contributes to tumour initiation progression. Inactivation PIN1 function conversely curbs growth cancer stem cell expansion, restores chemosensitivity blocks metastatic spread, thus providing rationale for therapeutic strategy based on inhibition. Notwithstanding, potent inhibitors are still missing from arsenal anti-cancer drugs. By...
Abstract Restoring antigen presentation for efficient and durable activation of tumor-specific CD8+ T-cell responses is pivotal to immunotherapy, yet the mechanisms that cause subversion dendritic cell (DC) functions are not entirely understood, limiting development targeted approaches. In this study, we show bona fide DCs resident in lung tumor tissues or exposed factors derived from whole tumors become refractory endosomal cytosolic sensor stimulation fail secrete IL12 IFNI....
Abstract Cross-presentation by type 1 DCs (cDC1) is critical to induce and sustain antitumoral CD8 T cell responses model antigens, in various tumor settings. However, the impact of cross-presenting cDC1 potential DC-based therapies tumors carrying varied levels bona-fide neoantigens (neoAgs) remain unclear. Here we develop a hypermutated non-small lung cancer female mice, encoding genuine MHC-I neoepitopes study neoAgs-specific spontaneous settings upon Flt3L + αCD40 (DC-therapy). We find...
Abstract Spectral libraries fulfill multiple functions in biological and analytical applications. For biologists, these provide a valuable resource to verify the presence abundance of proteins or pathways within selected cell type thus determine feasibility further experiments. Despite advances, existing are incomplete researchers only limited amount information. To address this, we introduce reference database - Library Immune Cells (SpLICe), covering B-cells, CD4 CD8 T-cells, macrophages...
Abstract The initiation of adaptive immune responses requires the direct interaction dendritic cells (DCs) with naive T lymphocytes. It is well established that maturation state DCs has a critical impact on outcome response. We show here mature form stable conjugates and induce formation organized synapses. Immature DCs, in contrast, few no A dynamic analysis revealed can long-lasting interactions cells, even absence Ag. only short intermittent contacts, suggesting premature termination...
Laser therapy, recently renamed as photobiomodulation, stands a promising supportive treatment for oral mucositis induced by oncological therapies. However, its mechanisms of action and, more importantly, safety in cancer patients, are still unclear. Here we explored the anti-cancer effect 3 laser protocols, set at most commonly used wavelengths, B16F10 melanoma and carcinogenesis mouse models. While light increased cell metabolism cultured cells, vivo outcome was reduced tumor progression....
Abstract Acquisition of cell-associated tumor antigens by type 1 dendritic cells (cDC1) is essential to induce and sustain specific CD8 + T via cross-presentation. Here we show that capture engulfment cell associated tissue resident lung cDC1 inhibited during progression mouse tumors. Mechanistically, loss phagocytosis linked tumor-mediated downregulation the phosphatidylserine receptor TIM4, highly expressed in normal cDC1. TIM4 blockade conditional deletion impair activation promote...
Lung tumor-infiltrating neutrophils are known to support growth and dissemination of cancer cells suppress T cell responses. However, the precise impact tissue on programming differentiation anticancer CD8 in vivo remains poorly understood. Here, we identified cell-autonomous secretion CXCL5 as sufficient drive infiltration mature, protumorigenic a mouse model non-small lung (NSCLC). Consistently, transcripts correlate with neutrophil density poor prognosis large human adenocarcinoma...
TIM4 has previously been associated with antitumor immunity, yet the pattern of expression and function this receptor across human cancer tissues remain poorly explored. Here we combined extensive immunolabeling in silico analysis pan-cancer transcriptomic data sets to explore clinical significance expression. Our results unveil that is expressed on a fraction cavity macrophages (CATIM4+MΦ) carcinoma patients. Moreover, uncover high T-cell zone carcinoma-associated tertiary lymphoid...
Receptors controlling the cross-presentation of tumor antigens by macrophage subsets in cancer tissues are poorly explored. Here, we show that TIM4
The immune synapse (IS) forms as dendritic cells (DCs) and T interact in lymph nodes during initiation of adaptive immunity. Factors that contribute to the formation maintenance IS stability function have been mostly studied cells, whereas little is known about events occurring DCs. Here, we show DCs activated by Toll-like receptor (TLR) agonists reorient microtubule-organizing center (MTOC) toward interacting cell antigen-specific through a mechanism depends on Rho GTPase Cdc42. IL-12,...
Abstract The Wiskott-Aldrich syndrome protein (WASp) is a key regulator of actin polimerization in hematopoietic cells. Mutations WASp cause severe immunodeficiency characterized by defective initiation primary immune response and autoimmunity. contribution altered dendritic cells (DCs) functions to the disease pathogenesis has not been fully elucidated. In this study, we show that conventional DCs develop normally WASp-deficient mice. However, Ag targeting lymphoid organ-resident via...
Mutations in Wiskott-Aldrich syndrome (WAS) protein (WASp), a regulator of actin dynamics hematopoietic cells, cause WAS, an X-linked primary immunodeficiency characterized by recurrent infections and marked predisposition to develop autoimmune disorders. The mechanisms that link alterations the phenotype are still poorly understood. We show chronic activation plasmacytoid dendritic cells (pDCs) elevated type-I interferon (IFN) levels play role WAS autoimmunity. patients display increased...
Interleukin-12 (IL-12), produced by dendritic cells in response to activation, is central pathogen eradication and tumor rejection. The trafficking pathways controlling spatial distribution intracellular transport of IL-12 vesicles the cell surface are still unknown. Here, we show that localizes late endocytic marked SNARE VAMP7. Dendritic (DCs) from VAMP7-deficient mice partially impaired multidirectional release IL-12. Upon encounter with antigen-specific T cells, IL-12-containing rapidly...
Abstract CCRL2 is a nonsignaling seven-transmembrane domain receptor. binds chemerin, protein that promotes chemotaxis of leukocytes, including macrophages and natural killer (NK) cells. In addition, controls the inflammatory response in different pathologic settings, such as hypersensitivity, arthritis, experimental autoimmune encephalitis. Here, we investigated role regulation lung cancer–related inflammation. The genetic deletion Ccrl2 promoted tumor progression urethane-induced...
Conventional type 1 dendritic cells (cDC1) are critical regulators of anti-tumoral T-cell responses. The structure and abundance intercellular contacts between cDC1 CD8 T in cancer tissues is important to determine the outcome response. However, molecular determinants controlling stability cDC1–CD8 interactions during progression remain poorly investigated. Here, we generated a genetic model non-small cell lung crossed fluorescent reporter (KP-XCR1venus) allow detection cDC1-CD8T clusters...