A5024623296- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Virus-based gene therapy research
- Cytokine Signaling Pathways and Interactions
- T-cell and B-cell Immunology
- Cancer Research and Treatments
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Cell Adhesion Molecules Research
- Chemokine receptors and signaling
- Immunodeficiency and Autoimmune Disorders
- Lung Cancer Treatments and Mutations
- Viral Infectious Diseases and Gene Expression in Insects
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Tuberculosis Research and Epidemiology
- Phagocytosis and Immune Regulation
- Tuberous Sclerosis Complex Research
- Mycorrhizal Fungi and Plant Interactions
- Cystic Fibrosis Research Advances
- Mycobacterium research and diagnosis
- Immune cells in cancer
- Cancer-related gene regulation
- PI3K/AKT/mTOR signaling in cancer
- Neuroinflammation and Neurodegeneration Mechanisms
Vita-Salute San Raffaele University
2014-2024
Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
2016-2024
Istituti di Ricovero e Cura a Carattere Scientifico
2016-2024
IRCCS Ospedale San Raffaele
2022
Interactions Arbres-Microorganismes
2019-2022
European Institute of Oncology
2020
Università Campus Bio-Medico
2018
Charité - Universitätsmedizin Berlin
2013
Max Delbrück Center
2013
San Raffaele University of Rome
2004-2013
Muscle injury induces a classical inflammatory response in which cells of the innate immune system rapidly invade tissue. Macrophages are prominently involved this and required for proper healing, as they known to be important clearing cellular debris supporting satellite cell differentiation. Here, we sought assess role adaptive muscle regeneration after acute damage. We show that T lymphocytes transiently recruited into damage appear exert pro-myogenic effect on repair. observed decrease...
Abstract Proliferation of Ag-specific T cells is central to the development protective immunity. The concomitant stimulation TCR and CD28 programs resting IL-2-driven clonal expansion. We report that a prolonged occupancy bypasses need for autocrine IL-2 secretion sustains IL-2-independent lymphocyte proliferation. In contrast, short engagement only drives expansion capable production. TCR/CD28- proliferation revealed different requirement PI3K mammalian target rapamycin (mTOR). Thus, both...
Abstract Resistance and tolerance mechanisms participate to the interplay between host pathogens. IL-17-mediated response has been shown be crucial for resistance respiratory infections, whereas its role in during chronic airway colonization is still unclear. Here, we investigated whether modulates of airways infection by P. aeruginosa . First, found that IL-17A levels were sustained mice at both early advanced stages confirmed these observations human samples from cystic fibrosis patients...
Purpose: Irregular blood flow and endothelial cell anergy, which characterize many solid tumors, hinder tumor infiltration by cytotoxic T lymphocytes (CTL). This confers resistance to cancer immunotherapy with monoclonal antibodies directed against regulatory pathways in (i.e., immune checkpoint blockade, ICB). We investigated whether NGR-TNF, a TNF derivative capable of targeting the vasculature, improving intratumor activated CTLs, could sensitize tumors ICB specific for PD-1 CTLA-4...
Genetic programs promoting cell cycle progression, DNA repair, and survival are coordinately induced in developing T cells require rapid turnover of effector molecules. As the COP9 signalosome (CSN) has been placed at crossroads these lower organisms, we addressed its role by conditionally deleting CSN5/JAB1, catalytic subunit, thymocytes. CSN5/JAB1(del/del) thymocytes show defective S phase progression massive apoptosis double-negative (DN) 4-double-positive (DP) transition stage, which is...
Epigenetic silencing of promoter and enhancer regions is a common phenomenon in malignant cells. The transcription factor STAT3 aberrantly activated several tumors, where its constitutive acetylation accounts for the transcriptional repression number tumor suppressor genes (TSG) via molecular mechanisms that remain to be understood. Using nucleophosmin-anaplastic lymphoma kinase-positive (NPM-ALK+) anaplastic large-cell (ALCL) as model system, we found cells patient-derived xenografts...
We have previously shown that chymotrypsin-cleaved soluble uPAR (D2D388-274) elicits migration of monocytic cells through interaction with FPRL-1, a G protein-coupled receptor is homologous to the fMLP receptor. Here, we report D2D388-274 also modulates ability monocytes migrate in response other chemokines. Pretreatment increasing amounts prevents cell MCP-1, RANTES and fMLP. demonstrate does not inhibit MCP-1 binding, elicit CCR2 internalization prevent MCP-1-induced intracellular Ca2+...
Lysosomal β-galactosylceramidase deficiency results in demyelination and inflammation the nervous system causing neurological Krabbe disease. In Twitcher mouse model of this disease, we found that symptoms parallel progressive severe lymphopenia. Although lymphopoiesis is normal before disease onset, primary secondary lymphoid organs progressively degenerate afterward. This occurs despite preserved erythropoiesis leads to peripheral lymphopenia caused by reduced numbers T cell precursors...
Abstract The clinical use of interleukin‐12 (IL12), a cytokine endowed with potent immunotherapeutic anticancer activity, is limited by systemic toxicity. hypothesis addressed that gold nanoparticles tagged tumor‐homing peptide containing isoDGR, an αvβ3‐integrin binding motif, can be exploited for delivering IL12 to tumors and improving its therapeutic index. To this aim, nanospheres are functionalized the head‐to‐tail cyclized‐peptide CGisoDGRG (Iso1) murine IL12. resulting nanodrug...
This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating potential early treatment with oral semaglutide. A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals T2D. scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, physician judgments on appropriateness. Participants completed anonymous...
Neural stem cells (NSCs) display tissue trophic and immune modulatory therapeutic activities after transplantation in central nervous system disorders. The intercellular interplay between target is increased NSCs exposed to inflammatory cues. Here, we hypothesize that cytokine signalling leads metabolic reprogramming of regulating some their effects. NSC lines were prepared from the subventricular zone (SVZ) 7–12-week-old mice. Whole secretome-based screening analysis intracellular small...
Abstract Ag encounter in the absence of proliferation results establishment T cell unresponsiveness, also known as clonal anergy. Anergic cells fail to proliferate upon restimulation because inability produce IL-2 and properly regulate G1 cycle checkpoint. Because optimal TCR CD28 engagement can elicit IL-2-independent progression, we investigated whether CD3/CD28-mediated activation anergic could overcome block, drive proliferation, thus reverse We show here that although antigenic...
Prep1 is a homeodomain transcription factor that acts by dimerizing with Pbx. Since null embryos die at gastrulation, we studied Prep1(i/i) hypomorphic mice to study the physiological role of Prep1. A low percentage homozygous survived birth, and their postnatal functions could be investigated. Reduced expression caused an abnormal thymic T-cell development: increased CD4(-) CD8(-) double-negative thymocytes, decrease in alphabetaTCR(high) cells (cells high levels alphabetaTau-cell receptor...
Donor-derived allogeneic T cells evoke potent graft versus tumor (GVT) effects likely due to the simultaneous recognition of tumor-specific and host-restricted minor histocompatibility (H) antigens. Here we investigated whether such could be reproduced in autologous settings by TCR gene-engineered lymphocytes. We report that redirected either a broadly expressed Y-encoded H antigen or tumor-associated antigen, although poorly effective if individually transferred, when simultaneously...
The ribonuclease DIS3 is one of the most frequently mutated genes in hematological cancer multiple myeloma, yet basis its tumor suppressor function this disease remains unclear. Herein, exploiting TCGA dataset, we found that plays a prominent role DNA damage response. inactivation causes genomic instability by increasing mutational load, and pervasive accumulation DNA:RNA hybrids induces double-strand breaks (DSBs). hybrid also prevents binding homologous recombination (HR) machinery to...
Abstract The Sin3 transcriptional regulator homolog A (Sin3A) is the core member of a multiprotein chromatin‐modifying complex. Its inactivation at CD4/CD8 double‐negative stage halts further thymocyte development. Among various functions, Sin3A regulates STAT3 activity, central to differentiation Th17 cells active in inflammatory disorders and opportunistic infections. To investigate consequences conditional more mature precursors post‐thymic T cell, we have generated CD4‐Cre CD4‐CreER T2 F...
Abstract It is well established that tumours hinder both natural and vaccine‐induced tumour‐specific CD4 + T‐cell responses. Adoptive therapy has the potential to circumvent functional tolerance enhance anti‐tumour protective While protocols suitable for expansion of cytotoxic CD8 T cells are currently available, data on remain scarce. We report here sensitized tumour‐associated Ag in vivo , proliferate vitro response IL‐7 without need exogenous stimulation accumulate several folds while...
Abstract Background Immunotherapy based on checkpoint inhibitors is highly effective in mismatch repair deficient (MMRd) colorectal cancer (CRC). These tumors carry a high number of mutations, which are predicted to translate into wide array neoepitopes; however, systematic classification the neoantigen repertoire MMRd CRC lacking. Mass spectrometry peptidomics has demonstrated existence MHC class I associated peptides (MAPs) originating from non-coding DNA regions. Based these premises we...
Abstract Nonmyeloablative hematopoietic cell transplantation can cure patients with hematologic malignancies but has reported limited success against solid tumors. This is possibly because of profound peripheral tolerance mechanisms and/or suboptimal tumor recognition by effector T lymphocytes. We report that in mice developing spontaneous prostate cancer, nonmyeloablative minor histocompatibility mismatched stem transplantation, and donor lymphocyte infusion unmanipulated lymphocytes...
Abstract CD4+ helper T cells are critical for protective immune responses and yet suboptimally primed in response to tumors. Cell-based vaccination strategies under evaluation clinical trials but limited by the need derive antigen-presenting (APC) from patients or compatible healthy donors. To overcome these limitations, we developed cell–targeted synthetic microbead-based artificial APC (aAPC) used them activate lymphocytes specific a tumor-associated model antigen (Ag) directly naive...
The mammalian target of rapamycin (mTOR) controls T-cell differentiation in response to polarizing cytokines. We previously found that mTOR blockade by (RAPA) delays the G1-S cell cycle transition and lymphocyte proliferation. Here, we report both complex 1 2 are readily activated following TCR/CD28 engagement critical for early expression Ifng, Il4 Foxp3, effector T absence While inhibition division were evident at low doses RAPA, 2, Foxp3 expression, polarization required higher more...
Abstract Vaccination can synergize with transplantation of allogeneic hematopoietic stem cells to cure hematologic malignancies, but the basis for this synergy is not understood degree where such approaches could be effective treating solid tumors. We investigated issue in a transgenic mouse model prostate cancer treated by nonmyeloablative MHC-matched, single Y chromosome–encoded, or multiple minor histocompatibility antigen-mismatched cell preparation. Here, we report that tumor-directed...
Abstract Technical difficulties in tracking endogenous CD4 T lymphocytes have limited the characterization of tumor-specific cell responses. Using fluorescent MHC class II/peptide multimers, we defined fate Leishmania receptor for activated C kinase (LACK)-specific cells mice bearing LACK-expressing TS/A tumors. LACK-specific CD44highCD62Llow accumulated draining lymph nodes and had characteristics effector cells, secreting IL-2 IFN-γ upon Ag restimulation. Increased frequencies...
Abstract Patients with P. aeruginosa airways infection show markedly variable clinical phenotypes likely influenced by genetic backgrounds. Here, we investigated the cellular events involved in resistance and susceptibility to chronic using genetically distinct inbred mouse strains. As for patients, different murine genotypes revealed infection. When directly compared, resistant C3H/HeOuJ susceptible A/J strains immune responsiveness pathogen. In mice, IL17-producing cells rapidly...