25 results on '"Ingegnere, Tiziano"'
Search Results
2. PMN-MDSC are a new target to rescue graft-versus-leukemia activity of NK cells in haplo-HSC transplantation
- Author
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Tumino, Nicola, Besi, Francesca, Di Pace, Anna Laura, Mariotti, Francesca Romana, Merli, Pietro, Li Pira, Giuseppina, Galaverna, Federica, Pitisci, Angela, Ingegnere, Tiziano, Pelosi, Andrea, Quatrini, Linda, Munari, Enrico, Locatelli, Franco, Moretta, Lorenzo, and Vacca, Paola
- Published
- 2020
- Full Text
- View/download PDF
3. Analysis of the mechanisms regulating soluble PD-1 production and function in human NK cells
- Author
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Mariotti, Francesca Romana, primary, Ingegnere, Tiziano, additional, Landolina, Nadine, additional, Vacca, Paola, additional, Munari, Enrico, additional, and Moretta, Lorenzo, additional
- Published
- 2023
- Full Text
- View/download PDF
4. Selective delivery of doxorubicin by novel stimuli-sensitive nano-ferritins overcomes tumor refractoriness
- Author
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Fracasso, Giulio, Falvo, Elisabetta, Colotti, Gianni, Fazi, Francesco, Ingegnere, Tiziano, Amalfitano, Adriana, Doglietto, Giovanni Battista, Alfieri, Sergio, Boffi, Alberto, Morea, Veronica, Conti, Giamaica, Tremante, Elisa, Giacomini, Patrizio, Arcovito, Alessandro, and Ceci, Pierpaolo
- Published
- 2016
- Full Text
- View/download PDF
5. Molecular definition of group 1 innate lymphoid cells in the mouse uterus
- Author
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Filipovic, Iva, Chiossone, Laura, Vacca, Paola, Hamilton, Russell S., Ingegnere, Tiziano, Doisne, Jean-Marc, Hawkes, Delia A., Mingari, Maria Cristina, Sharkey, Andrew M., Moretta, Lorenzo, and Colucci, Francesco
- Published
- 2018
- Full Text
- View/download PDF
6. End9: an early-passage cell line defective in master HLA-I transcriptional coordinators
- Author
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Tremante, Elisa, primary, Martayan, Aline, additional, Ingegnere, Tiziano, additional, Giorda, Ezio, additional, Allegretti, Matteo, additional, Giordani, Elena, additional, Messana, Katia, additional, Steimle, Viktor, additional, Kufer, Thomas, additional, Giacomini, Patrizio, additional, and Romania, Paolo, additional
- Published
- 2022
- Full Text
- View/download PDF
7. Current state and next-generation CAR-T cells in multiple myeloma
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Manier, Salomon, primary, Ingegnere, Tiziano, additional, Escure, Guillaume, additional, Prodhomme, Chloé, additional, Nudel, Morgane, additional, Mitra, Suman, additional, and Facon, Thierry, additional
- Published
- 2022
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- View/download PDF
8. IL-1R8 silencing improves the anti-tumor function of freshly isolated human NK cells
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Landolina, Nadine, primary, Mariotti, Francesca Romana, additional, Ingegnere, Tiziano, additional, Alicata, Claudia, additional, Ricci, Biancamaria, additional, Pelosi, Andrea, additional, Veneziani, Irene, additional, Azzarone, Bruno Giuseppe, additional, Garlanda, Cecilia, additional, Mantovani, Alberto, additional, Moretta, Lorenzo, additional, and Maggi, Enrico, additional
- Published
- 2022
- Full Text
- View/download PDF
9. Acute Myeloid Leukemia: Is It T Time?
- Author
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Ben Khoud, Meriem Ben, primary, Ingegnere, Tiziano, additional, Quesnel, Bruno, additional, Mitra, Suman, additional, and Brinster, Carine, additional
- Published
- 2021
- Full Text
- View/download PDF
10. An Anti-inflammatory microRNA Signature Distinguishes Group 3 Innate Lymphoid Cells From Natural Killer Cells in Human Decidua
- Author
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Pelosi, Andrea, primary, Alicata, Claudia, additional, Tumino, Nicola, additional, Ingegnere, Tiziano, additional, Loiacono, Fabrizio, additional, Mingari, Maria Cristina, additional, Moretta, Lorenzo, additional, and Vacca, Paola, additional
- Published
- 2020
- Full Text
- View/download PDF
11. PMN-MDSC are a new target to rescue graft-versus-leukemia activity of NK cells in haplo-HSC transplantation
- Author
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Tumino, Nicola, primary, Besi, Francesca, additional, Di Pace, Anna Laura, additional, Mariotti, Francesca Romana, additional, Merli, Pietro, additional, Li Pira, Giuseppina, additional, Galaverna, Federica, additional, Pitisci, Angela, additional, Ingegnere, Tiziano, additional, Pelosi, Andrea, additional, Quatrini, Linda, additional, Munari, Enrico, additional, Locatelli, Franco, additional, Moretta, Lorenzo, additional, and Vacca, Paola, additional
- Published
- 2019
- Full Text
- View/download PDF
12. Human CAR NK Cells: A New Non-viral Method Allowing High Efficient Transfection and Strong Tumor Cell Killing
- Author
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Ingegnere, Tiziano, primary, Mariotti, Francesca Romana, additional, Pelosi, Andrea, additional, Quintarelli, Concetta, additional, De Angelis, Biagio, additional, Tumino, Nicola, additional, Besi, Francesca, additional, Cantoni, Claudia, additional, Locatelli, Franco, additional, Vacca, Paola, additional, and Moretta, Lorenzo, additional
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- 2019
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- View/download PDF
13. PD-1 in human NK cells: evidence of cytoplasmic mRNA and protein expression
- Author
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Mariotti, Francesca R., primary, Petrini, Stefania, additional, Ingegnere, Tiziano, additional, Tumino, Nicola, additional, Besi, Francesca, additional, Scordamaglia, Francesca, additional, Munari, Enrico, additional, Pesce, Silvia, additional, Marcenaro, Emanuela, additional, Moretta, Alessandro, additional, Vacca, Paola, additional, and Moretta, Lorenzo, additional
- Published
- 2018
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- View/download PDF
14. 'Markers and function of human NK cells in normal and pathological conditions.'
- Author
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Del Zotto, Genny, Marcenaro, Emanuela, Vacca, Paola, Sivori, Simona, Pende, Daniela, DELLA CHIESA, Mariella, Moretta, Francesca, Ingegnere, Tiziano, Mingari, MARIA CRISTINA, Moretta, Alessandro, and Moretta, Lorenzo
- Subjects
Cytotoxicity, Immunologic ,Histology ,immune monitoring ,immunophenotypin ,viral infections ,innate lymphoid cells ,Graft vs Host Disease ,immune check-points ,immunophenotyping ,Bone marrow transplant, cancer, cell biology, flow cytometry, haploidentical stem cell transplantation, immune check points, immune monitoring, immunophenotypin ,immunotherapy, innate lymphoid cells, natural killer cells, viral infections, Animals, Graft vs Host Disease, Humans, Killer Cells, Natural, Leukemia, Phenotype, Receptors, KIR, Hematopoietic Stem Cell Transplantation, 2734, Histology, Cell Biology ,Receptors ,cell biology ,Animals ,Killer Cells ,cancer ,Humans ,Leukemia ,natural killer cells ,Hematopoietic Stem Cell Transplantation ,bone marrow transplant ,immune check points ,Flow Cytometry ,KIR ,Killer Cells, Natural ,Phenotype ,Natural ,flow cytometry ,haploidentical stem cell transplantation ,immunotherapy ,Biomarkers - Published
- 2017
15. Molecular definition of group 1 innate lymphoid cells in the mouse uterus
- Author
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Filipovic, Iva, primary, Chiossone, Laura, additional, Vacca, Paola, additional, Hamilton, Russell S, additional, Ingegnere, Tiziano, additional, Doisne, Jean-Marc, additional, Hawkes, Delia A, additional, Mingari, Maria Cristina, additional, Sharkey, Andrew, additional, Moretta, Lorenzo, additional, and Colucci, Francesco, additional
- Published
- 2018
- Full Text
- View/download PDF
16. TRF1 and TRF2 binding to telomeres is modulated by nucleosomal organization
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Galati, Alessandra, Micheli, Emanuela, Alicata, Claudia, Ingegnere, Tiziano, Cicconi, Alessandro, Pusch, Miriam Caroline, Giraud Panis, Marie Josèphe, Gilson, Eric, Cacchione, Stefano, Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
- Subjects
Binding Sites ,[SDV]Life Sciences [q-bio] ,Gene regulation, Chromatin and Epigenetics ,TRF2 ,DNA ,TRF1 ,Telomere ,Chromatin ,Nucleosomes ,Protein Structure, Tertiary ,Histones ,Telomere, Nucleosome, Chromatin, Telomeric Chromatin, TRF1, TRF2 ,Nucleosome ,Telomeric Chromatin ,Telomeric Repeat Binding Protein 2 ,Telomeric Repeat Binding Protein 1 ,ComputingMilieux_MISCELLANEOUS ,Protein Binding ,Repetitive Sequences, Nucleic Acid - Abstract
The ends of eukaryotic chromosomes need to be protected from the activation of a DNA damage response that leads the cell to replicative senescence or apoptosis. In mammals, protection is accomplished by a six-factor complex named shelterin, which organizes the terminal TTAGGG repeats in a still ill-defined structure, the telomere. The stable interaction of shelterin with telomeres mainly depends on the binding of two of its components, TRF1 and TRF2, to double-stranded telomeric repeats. Tethering of TRF proteins to telomeres occurs in a chromatin environment characterized by a very compact nucleosomal organization. In this work we show that binding of TRF1 and TRF2 to telomeric sequences is modulated by the histone octamer. By means of in vitro models, we found that TRF2 binding is strongly hampered by the presence of telomeric nucleosomes, whereas TRF1 binds efficiently to telomeric DNA in a nucleosomal context and is able to remodel telomeric nucleosomal arrays. Our results indicate that the different behavior of TRF proteins partly depends on the interaction with histone tails of their divergent N-terminal domains. We propose that the interplay between the histone octamer and TRF proteins plays a role in the steps leading to telomere deprotection.
- Published
- 2015
17. Role of ATR and ATM chinasis in telomers omeostasis
- Author
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Ingegnere, Tiziano and Palitti, Fabrizio
- Subjects
BIO/11 ,ATR ,ATM ,Telomeri - Abstract
I telomeri sono essenziali per fornire una struttura protettiva ”cap telomerico”, che difenda le estremità dei cromosomi lineari eucariotici. Se il “cap telomerico” viene perso i telomeri non possono più essere distinti dalle rotture a doppio filamento del DNA (DNA double-stranded breaks, DSBs). Evento che porta all’arresto del ciclo cellulare, fusioni telomeriche, e rapida degradazione delle estremità. Questa protezione è prevalentemente operata dal complesso proteico che lega specificamente il DNA telomerico (Shelterin). Recentemente è stato dimostrato come la mancanza di TRF1 porti i telomeri a somigliare a dei comuni siti fragili durante la replicazione del DNA. Ad ogni modo tutto il complesso shelterin è direttamente coinvolto nella protezione dei telomeri da eventi di fusione, ricombinazione e degradazione nucleolitica. Le protein-chinasi ATM e ATR giocano un ruolo centrale nel rilevare i danni al DNA ed innescare la risposta al danno. Entrambe risultano avere dei ruoli fondamentali nel mantenimento dei telomeri. Infatti nel modello murino in cui è indotta una perdita di funzione di ATM presentano invechiamento prematuro, indicante una inadeguata preservazione dei telomeri (Wong K.K., 2003). In uno studio condotto durante il ciclo cellulare è stata evidenziata l’importanza cruciale di ATM durante la fase G2 nel reclutare MRE11 e NBS1 (Verdun R.E. et al., 2005). Questi esperimenti suggeriscono che l’attivazione dei pathway del riparo del DNA, o di una parte di essi, non sia limitato ai telomeri con disfunzioni o particolarmente corti ma che sia una prassi generale e fondamentale per l’omeostasi telomerica. Nell’intento di indagare la funzione delle protein kinasi ATR e ATM in ambito telomerico si è proceduto ad inibire farmacologicamente Chk1, il principale effettore della risposta mediata da ATR, attraverso UCN-01 e ATM tramite KU55933. Questi due inibitori sono stati somministrati in 2 linee cellulari: Hela e Fibroblasti umani. I trattamenti sono stati eseguiti per 24h combinando anche il trattamento con Fluorodesossiuridina (FdU) un analogo delle basi azotate che provoca un rallentamento della forca replicativa. Analizzando i dati ottenuti con la PNA-FISH riscontriamo che l’inibizione farmacologica di ATM e di Chk1 non comporta l’aumento delle fusioni telomeriche. Visti gli inaspettati risultati ottenuti abbiamo voluto indagare se ci fossero differenze qualitative negli eventi di fusione. Per determinare l’importanza delle vie ATR e ATM –dipendenti in entrambe le tipologie di intermedi telomerici, abbiamo usato la Chromosome-orientation fluorescence in situ hybridization (CO-FISH). Non riscontriamo differenze sostanziali e significative tra il controllo e i trattamenti con i diversi inibitori. Per completare e confermare i risultati totalmente inaspettati dell’analisi citologica siamo andati ad indagare se il 3’overhang fosse stato alterato attraverso una tecnica sviluppata nel nostro laboratorio il T-OLA. Anche dopo l’inibizione di Chk1 o di ATM non abbiamo riscontrato perturbazioni nella lunghezza del 3’overhang. L’inibizione di Chk1 e di ATM nel nostro modello non sembra portare alla perturbazione della struttura protettiva del telomero. In alternativa ritroviamo che i nostri trattamenti sortiscono tutt’altro genere di effetti sui telomeri. Infatti riscontriamo un sostanziale aumento dei segnali telomerici multipli nelle Hela. Inoltre dimostriamo come i nostri inibitori portino all’aumento, dopo un singolo ciclo cellulare, di delezioni telomeriche sia sul singolo cromatide (sister chromatid loss) che su entrambi (telomere deletion). L’effetto è maggiormente pronunciato nei Fibroblasti. Anche se in letteratura non vengono associati tali eventi alla fragilità del telomero, in realtà tale comportamento, la rottura a seguito di stress replicativo, è tipica dei siti fragili. Siamo quindi andati a monitorare un sito fragile inducibile, somministrando i nostri trattamenti farmacologici, per cercare di comprendere meglio i risultati ottenuti. I risultati ottenuti con una linea linfoblastoide che porta la premutazione del sito FRAXA sono in parte sovrapponibili ai risultati ottenuti sui telomeri. Specialmente nelle Hela. Una possibile spiegazione di questa divergenza tra quanto osservato nei fibroblasti da una parte, e nelle Hela e 32B dall’altra, possa essere imputabile alla mancanza di una telomerasi attiva nei fibroblasti. L’interazione tra macchinario del riparo del DNA e telomeri è sempre più oggetto di attenzioni. Di notevole interesse è la comprensione del meccanismo che, come evidenziato anche dai nostri dati, porta proteine quali ATR e ATM a cambiare i target della propria azione. Infatti se è ormai evidente che ciò accada è pressoché sconosciuto il come avvenga e quali proteine medino tale cambiamento. Telomere integrity is essential to maintain chromosome stability and to avoid chromosome end fusion. Telomeres comprise tandem DNA repeats bound by a multiprotein complex known as shelterin. Sheltering contributes to maintenance of telomere integrity and prevents activation of DNA damage response (DDR) at telomeres. In particular it has been shown that TRF1 is important to prevent telomere breakage following replication fork stalling at telomeres. More recently, combined deletion of all the shelterin components revealed that this complex act to protect telomeres from a number of DNA-rearranging process including homologous recombination, NHEJ, ATM/ATR signaling and DNA resection. It has been shown that short dysfunctional telomeres activate DDRs mediated by ATM and ATR checkpoint kinases, which play a crucial role in the cellular response to DNA lesion. Paradoxically, ATR and ATM were found associated to telomeres in a cell cycle manner and in the absence of DNA damage, suggesting a role in the maintenance of telomere homeostasis. Indeed mice in which it was induced ATM loss of function show premature aging and have shorter telomeres than normal cells (Wong K.K., 2003). However, later studies failed to reveal a role of ATM in the elongation of short telomeres by telomerase (wong et al., 2003; Feldser et al 2006). More recently, it was demonstrated that severe reduction of ATR levels in primary murine fibroblasts, does not impair telomere length but induce the appearance of a number of futures typical of fragile sites. Similar finding was reported in murine cells lacking ATM (Qi et al 2003; wong et al., 2003). Collectively these results suggest that ATM and ATR participate to telomere protection in mammalian cells by preventing telomere fragility and recombination. In the effort to better understand the function of ATR and ATM in a telomeric context we respectively inhibited the proteins with UCN-01, an inhibitor of the Chk1 pathway responsive under ATR activation, and KU55933 a direct inhibitor of ATM. We tested this two inhibitor in Hela cells and human fibroblast. Furthermore, to induce a stalled DNA replication fork we added fluorodesossiuridine (FdU) in combination with the inhibitors. Here, we report by using telomere-fluorescence in situ hybridization (Telo-FISH) on metaphase chromosomes that in Hela cells and in human fibroblast both the inhibitors not seems to increase the telomere fusions. Via chromosome orientation-FISH we investigate if there are different involvement of the two protein in the type of chromosome fusions during the replication of leading and lagging strand. No differences are reported. With the Telomeric oligonucleotide ligation assay (T-OLA) we analyze the length of the 3’-overhang, the single strand region at the end of the telomeres. Our results show no difference of 3’-overhang length between control and the inhibitors treatment. Altogether this results seems to indicate that the inhibition by Chk1 and ATM pathway don’t affects the protective structure of telomeres. On the other hands we report a substantial increase of Multiple telomeric signal (MTS) in Hela cells but not in human fibroblast. We also show that the inhibition of Chk1 and ATM, mainly in Human fibroblast, lead to Telomere deletion (TD) and Sister Chromatid loss (SCL). Together these findings leads us to think that in absence of the ATM and ATR signaling telomeres resemble common fragile sites. In the effort to better understand our data we test our inhibitor on a common fragile site: FRAXA. The data from a linfoblastoid line with FRAXA, 32B, partially fit with the telomer’s one. Especially with Hela results. We suppose that the difference between Hela and 32B on one site, and Human Fibroblast on the other may be attributed to the lack of an active telomerase in Fibroblast. The attention for the interaction between DNA Repair Machinery and Telomer are growing in the scientific community. Particularly the mechanism that brings some protein, as ATM or ATR as we show, to remodelling their response in a telomeric context. Dottorato di ricerca in Evoluzione biologica e biochimica
- Published
- 2014
18. Sub-apoptotic dosages of pro-oxidant vitamin cocktails sensitize human melanoma cells to NK cell lysis
- Author
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Tremante, Elisa, primary, Santarelli, Lory, additional, Monaco, Elisa Lo, additional, Sampaoli, Camilla, additional, Ingegnere, Tiziano, additional, Guerrieri, Roberto, additional, Tomasetti, Marco, additional, and Giacomini, Patrizio, additional
- Published
- 2015
- Full Text
- View/download PDF
19. Monoclonal antibodies to HLA-E bind epitopes carried by unfolded β2m-free heavy chains
- Author
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Tremante, Elisa, primary, Lo Monaco, Elisa, additional, Ingegnere, Tiziano, additional, Sampaoli, Camilla, additional, Fraioli, Rocco, additional, and Giacomini, Patrizio, additional
- Published
- 2015
- Full Text
- View/download PDF
20. SMN affects membrane remodelling and anchoring of the protein synthesis machinery.
- Author
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Gabanella, Francesca, Pisani, Cinzia, Borreca, Antonella, Farioli-Vecchioli, Stefano, Ciotti, Maria Teresa, Ingegnere, Tiziano, Onori, Annalisa, Ammassari-Teule, Martine, Corbi, Nicoletta, Canu, Nadia, Monaco, Lucia, Passananti, Claudio, and Di Certo, Maria Grazia
- Subjects
MOTOR neurons ,SPLICEOSOMES ,PROTEIN synthesis ,NUCLEOPROTEINS ,MESSENGER RNA ,ENDOCYTOSIS - Abstract
Disconnection between membrane signalling and actin networks can have catastrophic effects depending on cell size and polarity. The survival motor neuron (SMN) protein is ubiquitously involved in assembly of spliceosomal small nuclear ribonucleoprotein particles. Other SMN functions could, however, affect cellular activities driving asymmetrical cell surface expansions. Genes able to mitigate SMN deficiency operate within pathways in which SMN can act, such as mRNA translation, actin network and endocytosis. Here, we found that SMN accumulates at membrane protrusions during the dynamic rearrangement of the actin filaments. In addition to localization data, we show that SMN interacts with caveolin-1, which mediates anchoring of translation machinery components. Importantly, SMN deficiency depletes the plasma membrane of ribosomes, and this correlates with the failure of fibroblasts to extend membrane protrusions. These findings strongly support a relationship between SMN and membrane dynamics. We propose that SMN could assembly translational platforms associated with and governed by the plasma membrane. This activity could be crucial in cells that have an exacerbated interdependence of membrane remodelling and local protein synthesis. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
21. Monoclonal antibodies to HLA-E bind epitopes carried by unfolded β2m-free heavy chains.
- Author
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Tremante, Elisa, Lo Monaco, Elisa, Ingegnere, Tiziano, Sampaoli, Camilla, Fraioli, Rocco, and Giacomini, Patrizio
- Abstract
Since HLA-E heavy chains accumulate free of their light β
2 -microglobulin (β2 m) subunit, raising mAbs to folded HLA-E heterodimers has been difficult, and mAb characterization has been controversial. Herein, mAb W6/32 and 5 HLA-E-restricted mAbs (MEM-E/02, MEM-E/07, MEM-E/08, DT9, and 3D12) were tested on denatured, acid-treated, and natively folded (both β2 m-associated and β2 m-free) HLA-E molecules. Four distinct conformations were detected, including unusual, partially folded (and yet β2 m-free) heavy chains reactive with mAb DT9. In contrast with previous studies, epitope mapping and substitution scan on thousands of overlapping peptides printed on microchips revealed that mAbs MEM-E/02, MEM-E/07, and MEM-E/08 bind three distinct α1 and α2 domain epitopes. All three epitopes are linear since they span just 4-6 residues and are 'hidden' in folded HLA-E heterodimers. They contain at least one HLA-E-specific residue that cannot be replaced by single substitutions with polymorphic HLA-A, HLA-B, HLA-C, HLA-F, and HLA-G residues. Finally, also the MEM-E/02 and 3D12 epitopes are spatially distinct. In summary, HLA-E-specific residues are dominantly immunogenic, but only when heavy chains are locally unfolded. Consequently, the available mAbs fail to selectively bind conformed HLA-E heterodimers, and HLA-E expression may have been inaccurately assessed in some previous oncology, reproductive immunology, virology, and transplantation studies. [ABSTRACT FROM AUTHOR]- Published
- 2015
- Full Text
- View/download PDF
22. Acute Myeloid Leukemia: Is It T Time?
- Author
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Khoud, Meriem Ben, Ingegnere, Tiziano, Quesnel, Bruno, Mitra, Suman, Brinster, Carine, and Funaro, Ada
- Subjects
- *
THYMUS physiology , *HOMEOSTASIS , *DISEASE progression , *ACUTE myeloid leukemia , *TREATMENT effectiveness , *BLOOD cells , *IMMUNITY , *T cells , *PHENOTYPES , *IMMUNOTHERAPY - Abstract
Simple Summary: Acute myeloid leukemia (AML) is a cancer characterized by impaired differentiation and excessive expansion of blood progenitor cells leading to their accumulation in the bone marrow and circulation. The aim of this review is to describe how these leukemic cells can influence the immune system, particularly T lymphocytes that originate from the thymus and are involved in cancers' and infections' eradication. We focus on the elderly population, as this disease mainly affects people over 60 years-old. We discuss how AML cells can modify T lymphocytes' production and functions. We also highlight newly developed therapeutic strategies to improve the anti-leukemic immune response and the clinical outcome of patients. Acute myeloid leukemia (AML) is a heterogeneous disease driven by impaired differentiation of hematopoietic primitive cells toward myeloid lineages (monocytes, granulocytes, red blood cells, platelets), leading to expansion and accumulation of "stem" and/or "progenitor"-like or differentiated leukemic cells in the bone marrow and blood. AML progression alters the bone marrow microenvironment and inhibits hematopoiesis' proper functioning, causing sustained cytopenia and immunodeficiency. This review describes how the AML microenvironment influences lymphoid lineages, particularly T lymphocytes that originate from the thymus and orchestrate adaptive immune response. We focus on the elderly population, which is mainly affected by this pathology. We discuss how a permissive AML microenvironment can alter and even worsen the thymic function, T cells' peripheral homeostasis, phenotype, and functions. Based on the recent findings on the mechanisms supporting that AML induces quantitative and qualitative changes in T cells, we suggest and summarize current immunotherapeutic strategies and challenges to overcome these anomalies to improve the anti-leukemic immune response and the clinical outcome of patients. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
23. PD-1 in human NK cells: evidence of cytoplasmic mRNA and protein expression.
- Author
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Mariotti, Francesca R., Petrini, Stefania, Ingegnere, Tiziano, Tumino, Nicola, Besi, Francesca, Scordamaglia, Francesca, Munari, Enrico, Pesce, Silvia, Marcenaro, Emanuela, Moretta, Alessandro, Vacca, Paola, and Moretta, Lorenzo
- Subjects
KILLER cells ,PROGRAMMED cell death 1 receptors ,PROTEIN expression ,ASCITIC fluids ,CONFOCAL microscopy - Abstract
Under physiological conditions, PD-1/PD-L1 interactions regulate unwanted over-reactions of immune cells and contribute to maintain peripheral tolerance. However, in tumor microenvironment, this interaction may greatly compromise the immune-mediated anti-tumor activity. PD-1
+ NK cells have been detected in high percentage in peripheral blood and ascitic fluid of ovarian carcinoma patients. To acquire information on PD-1 expression and physiology in human NK cells, we analyzed whether PD-1 mRNA and protein are present in resting, surface PD-1− , NK cells from healthy donors. Both different splicing isoforms of PD-1 mRNA and a cytoplasmic pool of PD-1 protein were detected. Similar results were obtained also from both in vitro-activated and tumor-associated NK cells. PD-1 mRNA and protein were higher in CD56dim than in CD56bright NK cells. Confocal microscopy analyses revealed that PD-1 protein is present in virtually all NK cells analyzed. The present findings are compatible with a rapid surface expression of PD-1 in NK cells in response to appropriate, still undefined, stimuli. [ABSTRACT FROM AUTHOR]- Published
- 2019
- Full Text
- View/download PDF
24. Monoclonal antibodies to HLA-E bind epitopes carried by unfolded β2 m-free heavy chains.
- Author
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Tremante E, Lo Monaco E, Ingegnere T, Sampaoli C, Fraioli R, and Giacomini P
- Subjects
- Antibodies, Monoclonal immunology, Cell Line, Epitope Mapping, Epitopes immunology, Histocompatibility Antigens Class I immunology, Humans, beta 2-Microglobulin immunology, HLA-E Antigens, Antibodies, Monoclonal chemistry, Epitopes chemistry, Histocompatibility Antigens Class I chemistry, Protein Folding, beta 2-Microglobulin chemistry
- Abstract
Since HLA-E heavy chains accumulate free of their light β2 -microglobulin (β2 m) subunit, raising mAbs to folded HLA-E heterodimers has been difficult, and mAb characterization has been controversial. Herein, mAb W6/32 and 5 HLA-E-restricted mAbs (MEM-E/02, MEM-E/07, MEM-E/08, DT9, and 3D12) were tested on denatured, acid-treated, and natively folded (both β2 m-associated and β2 m-free) HLA-E molecules. Four distinct conformations were detected, including unusual, partially folded (and yet β2 m-free) heavy chains reactive with mAb DT9. In contrast with previous studies, epitope mapping and substitution scan on thousands of overlapping peptides printed on microchips revealed that mAbs MEM-E/02, MEM-E/07, and MEM-E/08 bind three distinct α1 and α2 domain epitopes. All three epitopes are linear since they span just 4-6 residues and are "hidden" in folded HLA-E heterodimers. They contain at least one HLA-E-specific residue that cannot be replaced by single substitutions with polymorphic HLA-A, HLA-B, HLA-C, HLA-F, and HLA-G residues. Finally, also the MEM-E/02 and 3D12 epitopes are spatially distinct. In summary, HLA-E-specific residues are dominantly immunogenic, but only when heavy chains are locally unfolded. Consequently, the available mAbs fail to selectively bind conformed HLA-E heterodimers, and HLA-E expression may have been inaccurately assessed in some previous oncology, reproductive immunology, virology, and transplantation studies., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2015
- Full Text
- View/download PDF
25. TRF1 and TRF2 binding to telomeres is modulated by nucleosomal organization.
- Author
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Galati A, Micheli E, Alicata C, Ingegnere T, Cicconi A, Pusch MC, Giraud-Panis MJ, Gilson E, and Cacchione S
- Subjects
- Binding Sites, DNA metabolism, Histones metabolism, Nucleosomes chemistry, Protein Binding, Protein Structure, Tertiary, Repetitive Sequences, Nucleic Acid, Telomere chemistry, Telomeric Repeat Binding Protein 1 chemistry, Telomeric Repeat Binding Protein 2 chemistry, Nucleosomes metabolism, Telomere metabolism, Telomeric Repeat Binding Protein 1 metabolism, Telomeric Repeat Binding Protein 2 metabolism
- Abstract
The ends of eukaryotic chromosomes need to be protected from the activation of a DNA damage response that leads the cell to replicative senescence or apoptosis. In mammals, protection is accomplished by a six-factor complex named shelterin, which organizes the terminal TTAGGG repeats in a still ill-defined structure, the telomere. The stable interaction of shelterin with telomeres mainly depends on the binding of two of its components, TRF1 and TRF2, to double-stranded telomeric repeats. Tethering of TRF proteins to telomeres occurs in a chromatin environment characterized by a very compact nucleosomal organization. In this work we show that binding of TRF1 and TRF2 to telomeric sequences is modulated by the histone octamer. By means of in vitro models, we found that TRF2 binding is strongly hampered by the presence of telomeric nucleosomes, whereas TRF1 binds efficiently to telomeric DNA in a nucleosomal context and is able to remodel telomeric nucleosomal arrays. Our results indicate that the different behavior of TRF proteins partly depends on the interaction with histone tails of their divergent N-terminal domains. We propose that the interplay between the histone octamer and TRF proteins plays a role in the steps leading to telomere deprotection., (© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Published
- 2015
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