A5070619706- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Galectins and Cancer Biology
- Glycosylation and Glycoproteins Research
- Immune Response and Inflammation
- Protein Tyrosine Phosphatases
- Cutaneous lymphoproliferative disorders research
- Cancer Immunotherapy and Biomarkers
- Mast cells and histamine
- Cell Adhesion Molecules Research
- Synthesis and Biological Evaluation
- Immune cells in cancer
- Venous Thromboembolism Diagnosis and Management
- T-cell and Retrovirus Studies
- Urticaria and Related Conditions
- Infectious Diseases and Tuberculosis
- Atrial Fibrillation Management and Outcomes
- Infective Endocarditis Diagnosis and Management
- NF-κB Signaling Pathways
- Osteomyelitis and Bone Disorders Research
- Inflammatory Myopathies and Dermatomyositis
- Sphingolipid Metabolism and Signaling
Innate Pharma (France)
2013-2022
University of Genoa
2021
Australian National University
2002-2006
Australian Cancer Research Foundation
2002-2003
Centre d’Immunologie de Marseille-Luminy
1996-2001
Inserm
1996-2001
Aix-Marseille Université
2001
Institut Universitaire de France
1998-2001
Centre National de la Recherche Scientifique
1996-2000
Howard Hughes Medical Institute
1998
Natural killer (NK) cells contribute to a variety of innate immune responses viruses, tumors and allogeneic cells. However, our understanding NK cell biology is severely limited by the lack consensus phenotypic definition these across species, specific marker visualize them in situ , genetic model where may be selectively ablated. NKp46/CD335 an Ig-like superfamily surface receptor involved human activation. In addition human, we show here that NKp46 expressed all mouse strains analyzed, as...
<h3>Background</h3> Immunotherapies still fail to benefit colorectal cancer (CRC) patients. Relevant functional assays aimed at studying these failures and the efficacy of immunotherapy in human are scarce. 3D tumor cultures, called organoids or spheroids, represent interesting models study treatments could help challenge issues. <h3>Methods</h3> We analyzed heterotypic cocultures colon tumor-derived spheroids with immune cells assess infiltration, activation function T NK toward tumors...
Abstract NK cells express cell surface receptors for MHC class I proteins (KIR). Engagement of these inhibits cytotoxic programs. KIR can be expressed on T cells, and their engagement also results in inhibition effector functions initiated by the CD3/TCR complex. While human genes belong to Ig gene superfamily, mouse a family dimeric lectins. Despite distinct evolutionary origins, we show here that both HLA-Cw3-specific p58.183 H-2D d/k-specific Ly49A recruit same protein tyrosine...
An emerging family of cell surface inhibitory receptors is characterized by the presence intracytoplasmic immunoreceptor tyrosine-based inhibition motifs (ITIM). These ITIM-bearing receptors, which are typically paired with activating isoforms, associate Src homology domain 2-containing phosphatases following ITIM tyrosine phosphorylation. Two categories recruited receptors: protein-tyrosine phosphatases, SHP-1 and SHP-2, polyphosphate inositol 5-phosphatase, SHIP. The dynamic equilibrium B...
Natural killer cells are key of the innate immune system. cell receptor repertoires diversified by a stochastic expression killer-cell-immunoglobulin-like receptors and lectin-like such as NKG2 receptors. All individuals harbor subset natural expressing NKG2A, inhibitory checkpoint for HLA-E. Most neoplastic normal hematopoietic express HLA-E, ligand NKG2A. A novel anti-human NKG2A antibody induced tumor death, suggesting that could be useful in treatment cancers We found immunodeficient...
Natural killer cell and T subsets express at their surface a repertoire of receptors for MHC class I molecules, the natural (NKRs). NKRs are characterized by existence inhibitory activating isoforms, which encoded highly homologous but separate genes present in same locus. Inhibitory isoforms an intracytoplasmic immunoreceptor tyrosine-based inhibition motif, whereas lack any motif harbor charged amino acid residue transmembrane domain. We previously KARAP (killer receptor-associated...
Abstract Cross-talk between NK cells and dendritic (DCs) is critical for the potent therapeutic response to dsRNA, but receptors involved remained controversial. We show in this paper that two dsRNAs, polyadenylic-polyuridylic acid polyinosinic-polycytidylic [poly(I:C)], similarly engaged human TLR3, whereas only poly(I:C) triggered RIG-I MDA5. Both dsRNA enhanced cell activation within PBMCs induced IFN-γ. Although myeloid DCs (mDCs) were required activation, induction of cytolytic...
NK cell education is the process through which chronic engagement of inhibitory receptors by self MHC-I molecules preserves cellular responsiveness. The molecular mechanisms responsible for remain unclear. Here, we show that mouse associated with a higher basal activity mTOR/Akt pathway, commensurate to number educating receptors. This was dependent on SHP-1 phosphatase and essential improved responsiveness reactive cells. Upon stimulation, pathway amplified signaling activating enhancing...
Abstract Advanced cutaneous T-cell lymphoma (CTCL) remains an unmet medical need, which lacks effective targeted therapies. In this study, we report the development of IPH4102, a humanized monoclonal antibody that targets immune receptor KIR3DL2, is widely expressed on CTCL cells but few normal cells. Potent antitumor properties IPH4102 were documented in allogeneic human and mouse model KIR3DL2+ disease. activity was mediated by antibody-dependent cell cytotoxicity phagocytosis. improved...
Natural killer (NK) cells are lymphocytes of the innate immune system able to recognize and kill tumors lacking self-MHC class I molecules. This “missing-self” recognition is mediated by lack engagement MHC I-specific inhibitory NK cell receptors that include Ig-like (KIR) in humans Ly49 molecules mice. A promising immunotherapeutic strategy against + cancer block using monoclonal antibodies (mAb). However, interactions between their also required for acquisition functional competence, a...
The potential of the paired Ig-like receptors activating (PIR-A) and inhibitory (PIR-B) types for modifying an IgE antibody–mediated allergic response was evaluated in mouse bone marrow–derived mast cells. Although cells produced both PIR-A PIR-B, PIR-B found to be preferentially expressed on cell surface, where it constitutively tyrosine phosphorylated associated with intracellular SHP-1 protein phosphatase. coligation receptor (FcεRI) inhibited IgE-mediated activation release serotonin....
The potential of the paired Ig-like receptors activating (PIR-A) and inhibitory (PIR-B) types for modifying an IgE antibody–mediated allergic response was evaluated in mouse bone marrow–derived mast cells. Although cells produced both PIR-A PIR-B, PIR-B found to be preferentially expressed on cell surface, where it constitutively tyrosine phosphorylated associated with intracellular SHP-1 protein phosphatase. coligation receptor (FcεRI) inhibited IgE-mediated activation release serotonin....
Divergent hypotheses exist to explain how signaling by the B cell receptor (BCR) is initiated after antigen binding and it qualitatively altered in anergic cells selectively uncouple from nuclear factor κB c-Jun N-terminal kinase pathways while continuing activate extracellular signal–regulated calcium–nuclear of activated T pathways. Here we find that BCRs on are endocytosed at a very enhanced rate upon antigen, resulting large steady-state pool intracellularly sequestered receptors appear...
The number of circulating follicular B lymphocytes is normally kept within a precise range despite their dispersion through the body and daily overproduction precursors in bone marrow. By establishing genome wide recessive mutation screen C57BL/6 mice to identify critical components immune system regulation, we identified mutant strain with selective deficiency recirculating cells but not immature or peritoneal B1 cells. Analysis mixed marrow chimeras established that affects cell autonomous...