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  1. Article ; Online: CD4+ Regulatory T Cells in Human Cancer: Subsets, Origin, and Molecular Regulation.

    Swatler, Julian / De Luca, Marco / Rotella, Ivano / Lise, Veronica / Mazza, Emilia Maria Cristina / Lugli, Enrico

    Cancer immunology research

    2024  Volume 12, Issue 4, Page(s) 393–399

    Abstract: CD4+CD25hiFOXP3+ regulatory T cells (Treg) play major roles in the maintenance of immune tolerance, prevention of inflammation, and tissue homeostasis and repair. In contrast with these beneficial roles, Tregs are abundant in virtually all tumors and ... ...

    Abstract CD4+CD25hiFOXP3+ regulatory T cells (Treg) play major roles in the maintenance of immune tolerance, prevention of inflammation, and tissue homeostasis and repair. In contrast with these beneficial roles, Tregs are abundant in virtually all tumors and have been mechanistically linked to disease progression, metastases development, and therapy resistance. Tregs are thus recognized as a major target for cancer immunotherapy. Compared with other sites in the body, tumors harbor hyperactivated Treg subsets whose molecular characteristics are only beginning to be elucidated. Here, we describe current knowledge of intratumoral Tregs and discuss their potential cellular and tissue origin. Furthermore, we describe currently recognized molecular regulators that drive differentiation and maintenance of Tregs in cancer, with a special focus on those signals regulating their chronic immune activation, with relevant implications for cancer progression and therapy.
    MeSH term(s) Humans ; T-Lymphocytes, Regulatory ; Neoplasms/therapy ; Immune Tolerance ; Immunotherapy ; Inflammation
    Language English
    Publishing date 2024-04-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2732489-8
    ISSN 2326-6074 ; 2326-6066
    ISSN (online) 2326-6074
    ISSN 2326-6066
    DOI 10.1158/2326-6066.CIR-23-0517
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: CRUSTY: a versatile web platform for the rapid analysis and visualization of high-dimensional flow cytometry data.

    Puccio, Simone / Grillo, Giorgio / Alvisi, Giorgia / Scirgolea, Caterina / Galletti, Giovanni / Mazza, Emilia Maria Cristina / Consiglio, Arianna / De Simone, Gabriele / Licciulli, Flavio / Lugli, Enrico

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 5102

    Abstract: Flow cytometry (FCM) can investigate dozens of parameters from millions of cells and hundreds of specimens in a short time and at a reasonable cost, but the amount of data that is generated is considerable. Computational approaches are useful to identify ...

    Abstract Flow cytometry (FCM) can investigate dozens of parameters from millions of cells and hundreds of specimens in a short time and at a reasonable cost, but the amount of data that is generated is considerable. Computational approaches are useful to identify novel subpopulations and molecular biomarkers, but generally require deep expertize in bioinformatics and the use of different platforms. To overcome these limitations, we introduce CRUSTY, an interactive, user-friendly webtool incorporating the most popular algorithms for FCM data analysis, and capable of visualizing graphical and tabular results and automatically generating publication-quality figures within minutes. CRUSTY also hosts an interactive interface for the exploration of results in real time. Thus, CRUSTY enables a large number of users to mine complex datasets and reduce the time required for data exploration and interpretation. CRUSTY is accessible at https://crusty.humanitas.it/ .
    MeSH term(s) Flow Cytometry ; Algorithms ; Computational Biology ; Data Analysis
    Language English
    Publishing date 2023-09-04
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-40790-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Author Correction: Single-cell profiling defines the prognostic benefit of CD39

    Losurdo, Agnese / Scirgolea, Caterina / Alvisi, Giorgia / Brummelman, Jolanda / Errico, Valentina / Di Tommaso, Luca / Pilipow, Karolina / Colombo, Federico Simone / Fernandes, Bethania / Peano, Clelia / Testori, Alberto / Tinterri, Corrado / Roncalli, Massimo / Santoro, Armando / Mazza, Emilia Maria Cristina / Lugli, Enrico

    Communications biology

    2021  Volume 4, Issue 1, Page(s) 1252

    Language English
    Publishing date 2021-10-27
    Publishing country England
    Document type Published Erratum
    ISSN 2399-3642
    ISSN (online) 2399-3642
    DOI 10.1038/s42003-021-02789-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Chromosome positioning in interphase nuclei of hematopoietic stem cell and myeloid precursor.

    Lomiento, Mariana / Mammoli, Fabiana / Mazza, Emilia Maria Cristina / Bicciato, Silvio / Ferrari, Sergio

    Hematology reports

    2018  Volume 10, Issue 1, Page(s) 7515

    Abstract: Human myelopoiesis is an intriguing biological process during which multipotent stem cells limit their differentiation potential generating precursors that evolve into terminally differentiated cells. The differentiation process is correlated with ... ...

    Abstract Human myelopoiesis is an intriguing biological process during which multipotent stem cells limit their differentiation potential generating precursors that evolve into terminally differentiated cells. The differentiation process is correlated with differential gene expression and changes in nuclear architecture. In interphase, chromosomes are distinct entities known as chromosome territories and they show a radial localization that could result in a constrain of inter-homologous distance. This element plays a role in genome stability and gene expression. Here, we provide the first experimental evidence of 3D chromosomal arrangement considering two steps of human normal myelopoiesis. Specifically, multicolor 3D-FISH and 3D image analysis revealed that, in both normal human hematopoietic stem cells and myelod precursors CD14-, chromosomal position is correlated with gene density. However, we observed that inter-homologue distances are totally different during differentiation. This could be associated with differential gene expression that we found comparing the two cell types. Our results disclose an unprecedented framework relevant for deciphering the genomic mechanisms at the base of normal human myelopoiesis.
    Language English
    Publishing date 2018-04-03
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 2586645-X
    ISSN 2038-8330 ; 2038-8322
    ISSN (online) 2038-8330
    ISSN 2038-8322
    DOI 10.4081/hr.2018.7515
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Cell-Type-Specific Analysis of Molecular Pathology in Autism Identifies Common Genes and Pathways Affected Across Neocortical Regions.

    Velmeshev, Dmitry / Magistri, Marco / Mazza, Emilia Maria Cristina / Lally, Patrick / Khoury, Nathalie / D'Elia, Evan Ross / Bicciato, Silvio / Faghihi, Mohammad Ali

    Molecular neurobiology

    2020  Volume 57, Issue 5, Page(s) 2279–2289

    Abstract: Despite its heterogeneity, autism is characterized by a defined behavioral phenotype, suggesting that the molecular pathology affects specific neural substrates to cause behavioral dysfunction. Previous studies identified genes dysregulated in autism ... ...

    Abstract Despite its heterogeneity, autism is characterized by a defined behavioral phenotype, suggesting that the molecular pathology affects specific neural substrates to cause behavioral dysfunction. Previous studies identified genes dysregulated in autism cortex but did not address their cell-type specificity. Moreover, it is unknown whether there is a core of genes dysregulated across multiple neocortical regions. We applied RNA sequencing to postmortem brain tissue samples from autism patients and neurologically normal controls and combined our data with previously published datasets. We then identified genes, pathways, and alternative splicing events which are dysregulated in five neocortical regions in autism. To gain information about cell-type specificity of the dysregulated genes, we analyzed single-nuclei RNA sequencing data of adult human cortex and intersected cell-type-specific gene signatures with genes dysregulated in autism in specific cortical regions. We found that autism-associated gene expression changes across 4 frontal and temporal cortex regions converge on 27 genes related to immune response and enriched in human astrocytes, microglia, and brain endothelium. Shared splicing changes, however, are found in genes predominantly associated with synaptic function and adult interneurons and projection neurons. Finally, we demonstrate that regions of DNA differentially methylated in autism overlap genes associated with development and enriched in human cortical oligodendrocytes. Our study identifies signatures of autism molecular pathology shared across neocortical regions, as well as neural cell types enriched for common dysregulated genes, thus paving way for assessing cell-type-specific mechanisms of autism pathology.
    MeSH term(s) Alternative Splicing ; Autism Spectrum Disorder/genetics ; Autism Spectrum Disorder/pathology ; DNA Methylation ; Gene Expression Regulation ; Gene Ontology ; Humans ; Immunity/genetics ; Metabolic Networks and Pathways/genetics ; Neocortex/metabolism ; Neocortex/pathology ; Neuroglia/metabolism ; Neurons/metabolism ; Prefrontal Cortex/metabolism ; Prefrontal Cortex/pathology ; RNA, Messenger/analysis ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Sequence Analysis, RNA ; Single-Cell Analysis ; Synapses/metabolism ; Temporal Lobe/metabolism ; Temporal Lobe/pathology ; Transcriptome
    Chemical Substances RNA, Messenger
    Language English
    Publishing date 2020-02-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 645020-9
    ISSN 1559-1182 ; 0893-7648
    ISSN (online) 1559-1182
    ISSN 0893-7648
    DOI 10.1007/s12035-020-01879-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Author Correction

    Agnese Losurdo / Caterina Scirgolea / Giorgia Alvisi / Jolanda Brummelman / Valentina Errico / Luca Di Tommaso / Karolina Pilipow / Federico Simone Colombo / Bethania Fernandes / Clelia Peano / Alberto Testori / Corrado Tinterri / Massimo Roncalli / Armando Santoro / Emilia Maria Cristina Mazza / Enrico Lugli

    Communications Biology, Vol 4, Iss 1, Pp 1-

    Single-cell profiling defines the prognostic benefit of CD39high tissue resident memory CD8+ T cells in luminal-like breast cancer

    2021  Volume 1

    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2021-10-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Single-cell profiling defines the prognostic benefit of CD39high tissue resident memory CD8+ T cells in luminal-like breast cancer

    Agnese Losurdo / Caterina Scirgolea / Giorgia Alvisi / Jolanda Brummelman / Valentina Errico / Luca Di Tommaso / Karolina Pilipow / Federico Simone Colombo / Bethania Fernandes / Clelia Peano / Alberto Testori / Corrado Tinterri / Massimo Roncalli / Armando Santoro / Emilia Maria Cristina Mazza / Enrico Lugli

    Communications Biology, Vol 4, Iss 1, Pp 1-

    2021  Volume 11

    Abstract: Losurdo et al analyze breast cancer-infiltrating T cells by single-cell technologies . The find that the extent of infiltration of a small subset of tissue-resident memory CD8+ T cells identify patients with improved survival, highlighting the importance ...

    Abstract Losurdo et al analyze breast cancer-infiltrating T cells by single-cell technologies . The find that the extent of infiltration of a small subset of tissue-resident memory CD8+ T cells identify patients with improved survival, highlighting the importance of the specific T cell immune microenvironment.
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2021-09-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Single-cell profiling defines the prognostic benefit of CD39

    Losurdo, Agnese / Scirgolea, Caterina / Alvisi, Giorgia / Brummelman, Jolanda / Errico, Valentina / Di Tommaso, Luca / Pilipow, Karolina / Colombo, Federico Simone / Fernandes, Bethania / Peano, Clelia / Testori, Alberto / Tinterri, Corrado / Roncalli, Massimo / Santoro, Armando / Mazza, Emilia Maria Cristina / Lugli, Enrico

    Communications biology

    2021  Volume 4, Issue 1, Page(s) 1117

    Abstract: Luminal-like breast cancer (BC) constitutes the majority of BC subtypes, but, differently from highly aggressive triple negative BC, is poorly infiltrated by the immune system. The quality of the immune infiltrate in luminal-like BCs has been poorly ... ...

    Abstract Luminal-like breast cancer (BC) constitutes the majority of BC subtypes, but, differently from highly aggressive triple negative BC, is poorly infiltrated by the immune system. The quality of the immune infiltrate in luminal-like BCs has been poorly studied, thereby limiting further investigation of immunotherapeutic strategies. By using high-dimensional single-cell technologies, we identify heterogeneous behavior within the tissue-resident memory CD8+ T (Trm) cells infiltrating luminal-like tumors. A subset of CD127- CD39
    MeSH term(s) Apyrase/metabolism ; Breast Neoplasms/diagnosis ; Breast Neoplasms/genetics ; CD8-Positive T-Lymphocytes/metabolism ; Humans ; Prognosis ; Single-Cell Analysis
    Chemical Substances Apyrase (EC 3.6.1.5) ; ENTPD1 protein, human (EC 3.6.1.5)
    Language English
    Publishing date 2021-09-22
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2399-3642
    ISSN (online) 2399-3642
    DOI 10.1038/s42003-021-02595-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: TIM4 expression by dendritic cells mediates uptake of tumor-associated antigens and anti-tumor responses.

    Caronni, Nicoletta / Piperno, Giulia Maria / Simoncello, Francesca / Romano, Oriana / Vodret, Simone / Yanagihashi, Yuichi / Dress, Regine / Dutertre, Charles-Antoine / Bugatti, Mattia / Bourdeley, Pierre / Del Prete, Annalisa / Schioppa, Tiziana / Mazza, Emilia Maria Cristina / Collavin, Licio / Zacchigna, Serena / Ostuni, Renato / Guermonprez, Pierre / Vermi, William / Ginhoux, Florent /
    Bicciato, Silvio / Nagata, Shigekatzu / Benvenuti, Federica

    Nature communications

    2021  Volume 12, Issue 1, Page(s) 2237

    Abstract: Acquisition of cell-associated tumor antigens by type 1 dendritic cells (cDC1) is essential to induce and sustain tumor specific ... ...

    Abstract Acquisition of cell-associated tumor antigens by type 1 dendritic cells (cDC1) is essential to induce and sustain tumor specific CD8
    MeSH term(s) Adenocarcinoma/genetics ; Adenocarcinoma/immunology ; Animals ; Antigens, Neoplasm/genetics ; Antigens, Neoplasm/immunology ; CD8-Positive T-Lymphocytes/immunology ; Cross-Priming ; Dendritic Cells/immunology ; Humans ; Immunologic Surveillance ; Lung/immunology ; Lung Neoplasms/genetics ; Lung Neoplasms/immunology ; Membrane Proteins/genetics ; Membrane Proteins/immunology ; Mice
    Chemical Substances Antigens, Neoplasm ; Membrane Proteins ; TIM-4 protein, mouse
    Language English
    Publishing date 2021-04-14
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-021-22535-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Global chromatin conformation differences in the Drosophila dosage compensated chromosome X

    Koustav Pal / Mattia Forcato / Daniel Jost / Thomas Sexton / Cédric Vaillant / Elisa Salviato / Emilia Maria Cristina Mazza / Enrico Lugli / Giacomo Cavalli / Francesco Ferrari

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 16

    Abstract: In Drosophila, dosage compensation involves a twofold transcriptional upregulation of the single male chromosome X. Here the authors show that global conformational differences are specifically present in the male X chromosome and detectable using Hi-C ... ...

    Abstract In Drosophila, dosage compensation involves a twofold transcriptional upregulation of the single male chromosome X. Here the authors show that global conformational differences are specifically present in the male X chromosome and detectable using Hi-C data, indicating that dosage compensation affects global chromosome structure.
    Keywords Science ; Q
    Language English
    Publishing date 2019-11-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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