A5021452029- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Virus-based gene therapy research
- Cancer Immunotherapy and Biomarkers
- Cytokine Signaling Pathways and Interactions
- Cancer Research and Treatments
- Cell Adhesion Molecules Research
- Immunodeficiency and Autoimmune Disorders
- PI3K/AKT/mTOR signaling in cancer
- Chemokine receptors and signaling
- vaccines and immunoinformatics approaches
- Cancer, Stress, Anesthesia, and Immune Response
- Epigenetics and DNA Methylation
- Lung Cancer Treatments and Mutations
- Phagocytosis and Immune Regulation
- Viral Infectious Diseases and Gene Expression in Insects
- Estrogen and related hormone effects
- Protein Kinase Regulation and GTPase Signaling
- SARS-CoV-2 and COVID-19 Research
- RNA modifications and cancer
- Immune cells in cancer
- Cancer Cells and Metastasis
- Protease and Inhibitor Mechanisms
Vita-Salute San Raffaele University
2016-2025
Istituti di Ricovero e Cura a Carattere Scientifico
2016-2025
Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
2016-2025
San Raffaele University of Rome
2004-2025
IRCCS Ospedale San Raffaele
1992-2023
University of Turin
1988-2019
IRCCS Materno Infantile Burlo Garofolo
2017
Charité - Universitätsmedizin Berlin
2013
Max Delbrück Center
2013
Institute of Chemistry of Molecular Recognition
2013
The effects of inflammatory cytokines on naive T cells have been studied using MHC protein/peptide complexes microspheres, thus avoiding the use APCs whose functions may be affected by cytokines. IL-1, but not IL-12, increased proliferation CD4+ in response to Ag and IL-2, which is consistent with vivo priming cells. In contrast, CD8+ IL-2 required IL-12 replaced adjuvant stimulating an peptide. These results support a model distinct act directly provide third signal, along optimally...
Although lymphoid dendritic cells (DC) are thought to play an essential role in T cell activation, the initial physical interaction between antigen-bearing DC and antigen-specific has never been directly observed vivo under conditions where specificity of responding for relevant antigen could be unambiguously assessed. We used confocal microscopy track location fluorescent dye-labeled naive TCR transgenic CD4+ specific OVA peptide–I-Ad complex after adoptive transfer into syngeneic...
High mobility group box 1 (HMGB1) is an abundant chromatin protein that acts as a cytokine when released in the extracellular milieu by necrotic and inflammatory cells. Here, we show HMGB1 its receptor for advanced glycation end products (RAGE) induce both migration proliferation of vessel-associated stem cells (mesoangioblasts), thus may play role muscle tissue regeneration. In vitro, induces adult embryonic mesoangioblasts, disrupts barrier function endothelial monolayers. living mice,...
T cells activated by antigen receptor stimulation in the absence of accessory cell-derived costimulatory signals lose capacity to synthesize growth factor interleukin-2 (IL-2), a state called clonal anergy. An analysis CD3- and CD28-induced signal transduction revealed reduced ERK JNK enzyme activities murine anergic cells. The amounts proteins were unchanged, kinases could be fully presence phorbol 12-myristate 13-acetate. Dephosphorylation calcineurin substrate NFATp (preexisting nuclear...
Abstract Despite the wealth of information on signals required for T cell activation in vitro, generation functional Th cells vivo are poorly understood. We addressed this by directly tracking behavior adoptively transferred CD4+ TCR transgenic following Ag administration vivo. Injection soluble induced a transient accumulation Ag-specific lymphoid tissue. If bacterial LPS was present during period, enhanced numbers accumulated, migrated into B cell-rich follicles, and provided help Ab...
Phosphatidylinositol 3-kinase (PI 3-kinase) has been implicated as a participant in signaling pathways regulating cell growth by virtue of its activation response to various mitogenic stimuli. Here we describe the cloning novel and ubiquitously expressed human PI 3-kinase. The 4.8-kb cDNA encodes putative translation product 1,070 amino acids which is 42% identical bovine 28% Vps34, Saccharomyces cerevisiae involved vacuolar protein sorting. Human also similar Tor2, yeast required for cycle...
The adoptive transfer of naive CD4+ T cell receptor (TCR) transgenic cells was used to investigate the mechanisms by which adjuvant lipopolysaccharide (LPS) enhance clonal expansion in vivo. Subcutaneous administration soluble antigen (Ag) resulted rapid and transient accumulation Ag-specific draining lymph nodes (LNs), preceded production interleukin (IL)-2. CD28-deficient, produced only small amounts IL-2 response Ag did not accumulate LN same extent as wild-type cells. Injection LPS, a...
A small population of CD4+ OVA-specific TCR transgenic T cells was tracked following the induction peripheral tolerance by soluble Ag to address whether functionally unresponsive, or anergic cells, persist in vivo for extended periods time. Although injection OVA peptide absence adjuvant caused a transient expansion and deletion Ag-specific that showed signs prior activation persisted lymphoid tissues several months. These surviving had long-lasting, but reversible defects their ability...
Autophosphorylation sites of growth factor receptors with tyrosine kinase activity function as specific binding for Src homology 2 (SH2) domains signaling molecules. This interaction appears to be a crucial step in mechanism by which receptor kinases relay signals downstream pathways. Nck is widely expressed protein consisting exclusively SH2 and SH3 domains, the overexpression causes cell transformation. It has been shown that various factors stimulate phosphorylation its association...
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 In pancreatic ductal adenocarcinomas (PDAC), lymphoid infiltrates, comprised mainly of Th2 cells, predict a poor survival outcome in patients. IL4 signaling has been suggested to stabilize the phenotype this setting, but cellular source PDAC is unclear. Here, we show that basophils expressing are enriched tumor-draining lymph nodes (TDLN) Basophils present TDLNs correlated significantly with Th2/Th1 cell ratio tumors, where they served as an independent prognostic biomarker patient...
Abnormal tumor vasculature impairs T lymphocyte adhesion to endothelial cells and extravasation into neoplastic tissues, limiting the therapeutic potential of both active adoptive immunotherapies. We have found that treatment tumor-bearing mice with NGR-TNF, a Cys-Asn-Gly-Arg-Cys peptide-TNF fusion product capable altering barrier function improving drug penetration in tumors, associated intratumor upregulation leukocyte-endothelial cell molecules, release proinflammatory cytokines...
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...
Lymphatic endothelial cells (LECs) chemoattract naïve T and promote their survival in the lymph nodes, can cross-present antigens to CD8+ drive proliferation despite lacking key costimulatory molecules. However, functional consequence of LEC priming is unknown. Here, we show that while many proliferating LEC-educated enter early apoptosis, remainders comprise a long-lived memory subset, with transcriptional, metabolic, phenotypic features central stem cell-like cells. In vivo, these...
Abstract Inactivation of beta-2 microglobulin (B2M) is considered a determinant resistance to immune checkpoint inhibitors (ICPi) in melanoma and lung cancers. In contrast, B2M loss does not appear affect response ICPis mismatch repair–deficient (MMRd) colorectal tumors where biallelic inactivation frequently observed. We inactivated B2m multiple murine MMRd cancer models. Although cells would readily grow immunocompetent mice, null were tumorigenic regressed when treated with anti–PD-1...