PAROLINI SILVIA

Functional and expression analysis of new receptor molecules of human natural killer lymphocytes identified for the first time through the generation of monoclonal antibodies. ♣ Functional analysis of Natural Killer cells in patients with various primary immunodeficiencies: in particular, patients suffering from: - X-linked lymphoproliferative syndrome, with mutations of SAP (Slam Associated Protein) - Hermansky-Pudlak type 2 syndrome, - Wiskott-Aldrich syndrome (WAS) and WASP mutation - mutations of WIP (WASP interacting protein) - Pallidin protein mutations - mutations of Dock2 and Dock8 protein - mutations of NFKB2, NFKB1 - defects of STAT1, - mutations of PI3Ks (p85alfa) - mutations of RAG 1 and 2 (Recombinase-Activating Gene) and NHEJ proteins. - studies are ongoing in patients with severe immune disorders that include severe functional deficits of NK cells caused by mutations of molecules with an important role in the immune response (IKKa, RAC2, CTLA-4) and by unknown diseases and / or unknown genetic defects. ♣ Study of the role of human Natural Killer cells in the early phases of the immune response. Analysis of NK cell subsets from the peripheral blood and from secondary lymphoid tissues by cytofluorimetric, immunohistochemical and immunofluorescence analysis. ♣ Since 2006 we has been collaborating with the Innate Pharma S.A. Company / Biopharmaceutical Company, Marseille, France, which has expertise in the production of immunotherapeutic drugs for tumors and inflammatory diseases. ♣ Role of Natural Killer lymphocytes in patients with ovarian cancer. In recent years our research has focused on the functional mechanisms used by Natural Killer cells to recognize ovarian cancer cells. Epithelial ovarian cancer is the gynecological tumor with the highest mortality rate due to a high resistance to conventional therapies. In particular, the activating and inhibitory lymphocyte receptors were able to recognize expressed ligands, specifically from the autologous primary lines isolated from patients affected by ovarian cancer. We have identified some ligands that could be the cause of downregulation of activating receptors fundamental for the cytotoxic function of Natural Killer cells (B7 / H6, ligand of NKP30, and PRV and Nectin-2 ligands of DNAM-1) and ligands that would stimulate inhibitory receptors (PDL1 / 2 PD-1 ligands) expressed by certain histotypes of ovarian carcinoma. Such inhibitory receptors can prevent and block anti-tumor activity. Recently, in collaboration with the research group led by Prof. A. Moretta (DIMES, University of Genoa) we have identified a small subset of NK cells of peripheral blood of healthy donors that expresses the PD-1 inhibitor receptor (Programmed Death Receptor 1).