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PERSYST SIGNED

Generation and maintenance of long-lived memory T cells in humans

Total Cost €

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EC-Contrib. €

0

Partnership

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 PERSYST project word cloud

Explore the words cloud of the PERSYST project. It provides you a very rough idea of what is the project "PERSYST" about.

cells    fate    immune    recipient    subsequently    bone    basis    capability    transcriptional    somatic    samples    defining    requirement    tscm    levels    genome    superior    iuml    maintenance    tested    humans    persist    acquired    pool    gene    expression    adoptively    vivo    considerable    situations    durable    self    capacity    marrow    hosts    differentiation    arrest    infections    functional    stem    reconstituted    renewing    assumed    human    initially    regards    cancers    governing    indicate    humanized    limited    mechanisms    acquisition    showed    absence    effector    transplantation    renewal    persistence    primary    conventional    memory    generate    inhibit    tumor    na    multiple    cell    attributes    models    pivotal    single    molecular    expressed    formally    pathological    homeostasis    regulators    homeostatic    protective    candidate    regulate    failed    never    enhanced    shown    contrast    unexplored    antigen    mouse    mediated    regard    ve    technologies    antigenic    transferred    lived    demonstrated    physiological    senescence   

Project "PERSYST" data sheet

The following table provides information about the project.

Coordinator
HUMANITAS MIRASOLE SPA 

Organization address
address: VIA MANZONI 56
city: ROZZANO (MI)
postcode: 20100
website: www.humanitas.it

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Italy [IT]
 Total cost 1˙500˙000 €
 EC max contribution 1˙500˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-STG
 Funding Scheme ERC-STG
 Starting year 2015
 Duration (year-month-day) from 2015-09-01   to  2021-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    HUMANITAS MIRASOLE SPA IT (ROZZANO (MI)) coordinator 1˙500˙000.00

Map

 Project objective

Defining the molecular mechanisms governing memory T cell differentiation and homeostasis is of pivotal importance to generate durable and protective T cell responses against infections and cancers. Considerable knowledge in this regard has been acquired in mouse models but is still limited about human T cells. In particular, some mechanisms are assumed to occur in humans but were never formally demonstrated. We showed that memory T cells adoptively-transferred with bone marrow transplantation failed to persist in recipient hosts in the absence of antigen. By contrast, self/tumor-specific naïve T cells rapidly acquired T memory stem cell (TSCM) attributes and subsequently reconstituted the memory T cell pool by homeostatic differentiation. Current models indicate human TSCM cells as superior to conventional memory T cells in regards to effector potential and persistence capacity. Genome-wide expression analysis identified candidate TSCM cell-specific transcriptional regulators that were shown to inhibit senescence, promote self-renewal and regulate somatic differentiation. In this project, by using single cell technologies, primary human samples and in vivo humanized models, we will define the molecular mechanisms at the basis of memory T cell formation and maintenance in humans. We will initially define the antigenic requirement for the long-term persistence of memory T cells by following the fate of adoptively-transferred T cells. As the field remains unexplored, we will investigate the acquisition of memory attributes by self/tumor-specific T cells on multiple functional levels. The gene products specifically expressed by self-renewing TSCM cells will be finally tested for their capability to arrest T cell differentiation and generate long-lived memory T cells with enhanced stem cell-like properties. Our results will impact multiple physiological and pathological situations involving T cell-mediated immune responses.

 Publications

year authors and title journal last update
List of publications.
2019 Gabriele De Simone, Emilia M. C. Mazza, Antonino Cassotta, Alexey N. Davydov, Mirela Kuka, Veronica Zanon, Federica De Paoli, Eloise Scamardella, Maria Metsger, Alessandra Roberto, Karolina Pilipow, Federico S. Colombo, Elena Tenedini, Enrico Tagliafico, Luca Gattinoni, Domenico Mavilio, Clelia Peano, David A. Price, Satya P. Singh, Joshua M. Farber, Valentina Serra, Francesco Cucca, Francesco Fer
CXCR3 Identifies Human Naive CD8+ T Cells with Enhanced Effector Differentiation Potential
published pages: , ISSN: 0022-1767, DOI:
Journal of Immunology 2020-04-15
2020 Kared H, Tan SW, Lau MC, Chevrier M, Tan C, How W, Wong G, Strickland M, Malleret B, Amoah A, Pilipow K, Zanon V, Govern NM, Lum J, Chen JM, Lee B, Florian MC, Geiger H, Ginhoux F, Ruiz-Mateos E, Fulop T, Rajasuriar R, Kamarulzaman A, Ng TP, Lugli E, Larbi A.
Immunological history governs human stem cell memory CD4 heterogeneity via the Wnt signaling pathway
published pages: , ISSN: 2041-1723, DOI:
Nature Communications 2020-04-15
2017 Veronica Zanon, Karolina Pilipow, Eloise Scamardella, Federica De Paoli, Gabriele De Simone, David A. Price, Amaia Martinez Usatorre, Pedro Romero, Domenico Mavilio, Alessandra Roberto, Enrico Lugli
Curtailed T-cell activation curbs effector differentiation and generates CD8 + T cells with a naturally-occurring memory stem cell phenotype
published pages: 1468-1476, ISSN: 0014-2980, DOI: 10.1002/eji.201646732
European Journal of Immunology 47/9 2020-02-26
2018 Karolina Pilipow, Eloise Scamardella, Simone Puccio, Sanjivan Gautam, Federica De Paoli, Emilia M.C. Mazza, Gabriele De Simone, Sara Polletti, Marta Buccilli, Veronica Zanon, Pietro Di Lucia, Matteo Iannacone, Luca Gattinoni, Enrico Lugli
Antioxidant metabolism regulates CD8+ T memory stem cell formation and antitumor immunity
published pages: , ISSN: 2379-3708, DOI:
JCI Insight 2020-02-26
2018 Emilia Maria Cristina Mazza, Jolanda Brummelman, Giorgia Alvisi, Alessandra Roberto, Federica De Paoli, Veronica Zanon, Federico Colombo, Mario Roederer, Enrico Lugli
Background fluorescence and spreading error are major contributors of variability in high‐dimensional flow cytometry data visualization by t‐distributed stochastic neighboring embedding
published pages: , ISSN: 1552-4930, DOI:
Cytometry Part A 2020-02-26

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