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  1. Article ; Online: Modulation of the skin microbiome in cutaneous T-cell lymphoma delays tumour growth and increases survival in the murine EL4 model.

    Dey, Saptaswa / Vieyra-Garcia, Pablo Augusto / Joshi, Aaroh Anand / Trajanoski, Slave / Wolf, Peter

    Frontiers in immunology

    2024  Volume 15, Page(s) 1255859

    Abstract: Cutaneous T-cell lymphomas (CTCL) are a group of lymphoproliferative disorders of skin-homing T cells causing chronic inflammation. These disorders cause impairment of the immune environment, which leads to severe infections and/or sepsis due to ... ...

    Abstract Cutaneous T-cell lymphomas (CTCL) are a group of lymphoproliferative disorders of skin-homing T cells causing chronic inflammation. These disorders cause impairment of the immune environment, which leads to severe infections and/or sepsis due to dysbiosis. In this study, we elucidated the host-microbial interaction in CTCL that occurs during the phototherapeutic treatment regime and determined whether modulation of the skin microbiota could beneficially affect the course of CTCL. EL4 T-cell lymphoma cells were intradermally grafted on the back of C57BL/6 mice. Animals were treated with conventional therapeutics such as psoralen + UVA (PUVA) or UVB in the presence or absence of topical antibiotic treatment (neomycin, bacitracin, and polymyxin B sulphate) as an adjuvant. Microbial colonisation of the skin was assessed to correlate with disease severity and tumour growth. Triple antibiotic treatment significantly delayed tumour occurrence (
    MeSH term(s) Animals ; Microbiota/drug effects ; Mice ; Skin/microbiology ; Skin/pathology ; Skin/immunology ; Skin/drug effects ; Skin Neoplasms/microbiology ; Skin Neoplasms/immunology ; Skin Neoplasms/pathology ; Lymphoma, T-Cell, Cutaneous/microbiology ; Lymphoma, T-Cell, Cutaneous/pathology ; Lymphoma, T-Cell, Cutaneous/drug therapy ; Lymphoma, T-Cell, Cutaneous/therapy ; Mice, Inbred C57BL ; Disease Models, Animal ; Anti-Bacterial Agents/therapeutic use ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/administration & dosage ; Cell Line, Tumor ; Female ; Humans
    Chemical Substances Anti-Bacterial Agents
    Language English
    Publishing date 2024-04-05
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2024.1255859
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Extracorporeal Photopheresis: A Case of Immunotherapy Ahead of Its Time.

    Vieyra-Garcia, Pablo Augusto / Wolf, Peter

    Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie

    2020  Volume 47, Issue 3, Page(s) 226–235

    Abstract: Extracorporeal photopheresis (ECP) is a cell-based immunotherapy that involves the reinfusion of autologous leukocytes after exposure to psoralen and UVA. The treatment has been used for over 30 years, at first on patients with cutaneous T-cell lymphoma ( ...

    Abstract Extracorporeal photopheresis (ECP) is a cell-based immunotherapy that involves the reinfusion of autologous leukocytes after exposure to psoralen and UVA. The treatment has been used for over 30 years, at first on patients with cutaneous T-cell lymphoma (CTCL) and later for the management of patients with graft-versus-host disease (GvHD), sclerosing disorders, atopic dermatitis, and other diseases that may share the common driving factor of a pathogenic T-cell clone or clones in blood circulation. Patients with clinical improvement mount an antigen-specific immune response that may have tolerance traits in the case of GvHD or anticlonal cytotoxic characteristics in the case of CTCL. The exact mechanisms that dictate one response or the other are not fully understood, but the evidence accumulated so far indicates that multiple events occur simultaneously and consequentially contribute to the end result. These include contact of cells with the outside (plastics and tubing of the ECP apparatus), exposure to psoralen and UVA that activates platelets, monocytes, and other myeloid cells, the release of damage-associated molecular patterns, differentiation of monocytes into dendritic cells, and generation and successive presentation of numerous antigens after the phagocytosis of apoptotic cells. Once reintroduced, the ECP product increases the frequency and activity of regulatory T cells (Tregs), shifts the systemic cytokine balance, and promotes extravasation of immune cells that together shape the effects of this treatment. In this review, we summarize the seminal work and most recent literature of the therapeutic mechanisms and reflect on future avenues of improvements and applications of ECP.
    Language English
    Publishing date 2020-05-27
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2100848-6
    ISSN 1660-3818 ; 1660-3796
    ISSN (online) 1660-3818
    ISSN 1660-3796
    DOI 10.1159/000508479
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: The molecular and phenotypic makeup of fetal human skin T lymphocytes.

    Reitermaier, René / Ayub, Tanya / Staller, Julia / Kienzl, Philip / Fortelny, Nikolaus / Vieyra-Garcia, Pablo Augusto / Worda, Christof / Fiala, Christian / Staud, Clement / Eppel, Wolfgang / Scharrer, Anke / Krausgruber, Thomas / Elbe-Bürger, Adelheid

    Development (Cambridge, England)

    2021  Volume 149, Issue 8

    Abstract: The adult human skin contains a vast number of T cells that are essential for skin homeostasis and pathogen defense. T cells are first observed in the skin at the early stages of gestation; however, our understanding of their contribution to early ... ...

    Abstract The adult human skin contains a vast number of T cells that are essential for skin homeostasis and pathogen defense. T cells are first observed in the skin at the early stages of gestation; however, our understanding of their contribution to early immunity has been limited by their low abundance and lack of comprehensive methodologies for their assessment. Here, we describe a new workflow for isolating and expanding significant amounts of T cells from fetal human skin. Using multiparametric flow cytometry and in situ immunofluorescence, we found a large population with a naive phenotype and small populations with a memory and regulatory phenotype. Their molecular state was characterized using single-cell transcriptomics and TCR repertoire profiling. Importantly, culture of total fetal skin biopsies facilitated T cell expansion without a substantial impact on their phenotype, a major prerequisite for subsequent functional assays. Collectively, our experimental approaches and data advance the understanding of fetal skin immunity and potential use in future therapeutic interventions.
    MeSH term(s) Adult ; Female ; Fetus/cytology ; Fetus/immunology ; Flow Cytometry ; Humans ; Male ; Middle Aged ; Skin/cytology ; Skin/immunology ; T-Lymphocytes/cytology ; T-Lymphocytes/immunology
    Language English
    Publishing date 2021-10-26
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 90607-4
    ISSN 1477-9129 ; 0950-1991
    ISSN (online) 1477-9129
    ISSN 0950-1991
    DOI 10.1242/dev.199781
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  4. Article ; Online: αβγδ T cells play a vital role in fetal human skin development and immunity.

    Reitermaier, René / Krausgruber, Thomas / Fortelny, Nikolaus / Ayub, Tanya / Vieyra-Garcia, Pablo Augusto / Kienzl, Philip / Wolf, Peter / Scharrer, Anke / Fiala, Christian / Kölz, Marita / Hiess, Manuela / Vierhapper, Martin / Schuster, Christopher / Spittler, Andreas / Worda, Christof / Weninger, Wolfgang / Bock, Christoph / Eppel, Wolfgang / Elbe-Bürger, Adelheid

    The Journal of experimental medicine

    2021  Volume 218, Issue 4

    Abstract: T cells in human skin play an important role in the immune defense against pathogens and tumors. T cells are present already in fetal skin, where little is known about their cellular phenotype and biological function. Using single-cell analyses, we ... ...

    Abstract T cells in human skin play an important role in the immune defense against pathogens and tumors. T cells are present already in fetal skin, where little is known about their cellular phenotype and biological function. Using single-cell analyses, we identified a naive T cell population expressing αβ and γδ T cell receptors (TCRs) that was enriched in fetal skin and intestine but not detected in other fetal organs and peripheral blood. TCR sequencing data revealed that double-positive (DP) αβγδ T cells displayed little overlap of CDR3 sequences with single-positive αβ T cells. Gene signatures, cytokine profiles and in silico receptor-ligand interaction studies indicate their contribution to early skin development. DP αβγδ T cells were phosphoantigen responsive, suggesting their participation in the protection of the fetus against pathogens in intrauterine infections. Together, our analyses unveil a unique cutaneous T cell type within the native skin microenvironment and point to fundamental differences in the immune surveillance between fetal and adult human skin.
    MeSH term(s) Adult ; Cells, Cultured ; Cytokines/metabolism ; Fetus/immunology ; Healthy Volunteers ; Humans ; Immunologic Surveillance ; Intestines/embryology ; Intestines/immunology ; Middle Aged ; RNA-Seq/methods ; Receptors, Antigen, T-Cell, alpha-beta/genetics ; Receptors, Antigen, T-Cell, gamma-delta/genetics ; Single-Cell Analysis/methods ; Skin/embryology ; Skin/growth & development ; Skin/immunology ; T-Lymphocytes/immunology ; Transcriptome
    Chemical Substances Cytokines ; Receptors, Antigen, T-Cell, alpha-beta ; Receptors, Antigen, T-Cell, gamma-delta
    Language English
    Publishing date 2021-02-24
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218343-2
    ISSN 1540-9538 ; 0022-1007
    ISSN (online) 1540-9538
    ISSN 0022-1007
    DOI 10.1084/jem.20201189
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Quality of Life, Anxiety, and Depression in Patients With Early-Stage Mycosis Fungoides and the Effect of Oral Psoralen Plus UV-A (PUVA) Photochemotherapy on it.

    Graier, Thomas / Fink-Puches, Regina / Porkert, Stephanie / Lang, Roland / Pöchlauer, Sophie / Ratzinger, Gudrun / Tanew, Adrian / Selhofer, Sylvia / Sator, Paul-Gunther / Hofer, Angelika / Gruber-Wackernagel, Alexandra / Legat, Franz J / Vieyra-Garcia, Pablo Augusto / Quehenberger, Franz / Wolf, Peter

    Frontiers in medicine

    2020  Volume 7, Page(s) 330

    Abstract: Background: ...

    Abstract Background:
    Language English
    Publishing date 2020-08-05
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2775999-4
    ISSN 2296-858X
    ISSN 2296-858X
    DOI 10.3389/fmed.2020.00330
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  6. Article ; Online: Blocking STAT3/5 through direct or upstream kinase targeting in leukemic cutaneous T-cell lymphoma.

    Sorger, Helena / Dey, Saptaswa / Vieyra-Garcia, Pablo Augusto / Pölöske, Daniel / Teufelberger, Andrea R / de Araujo, Elvin D / Sedighi, Abootaleb / Graf, Ricarda / Spiegl, Benjamin / Lazzeri, Isaac / Braun, Till / Garces de Los Fayos Alonso, Ines / Schlederer, Michaela / Timelthaler, Gerald / Kodajova, Petra / Pirker, Christine / Surbek, Marta / Machtinger, Michael / Graier, Thomas /
    Perchthaler, Isabella / Pan, Yi / Fink-Puches, Regina / Cerroni, Lorenzo / Ober, Jennifer / Otte, Moritz / Albrecht, Jana D / Tin, Gary / Abdeldayem, Ayah / Manaswiyoungkul, Pimyupa / Olaoye, Olasunkanmi O / Metzelder, Martin L / Orlova, Anna / Berger, Walter / Wobser, Marion / Nicolay, Jan P / André, Fiona / Nguyen, Van Anh / Neubauer, Heidi A / Fleck, Roman / Merkel, Olaf / Herling, Marco / Heitzer, Ellen / Gunning, Patrick T / Kenner, Lukas / Moriggl, Richard / Wolf, Peter

    EMBO molecular medicine

    2022  Volume 14, Issue 12, Page(s) e15200

    Abstract: Leukemic cutaneous T-cell lymphomas (L-CTCL) are lymphoproliferative disorders of skin-homing mature T-cells causing severe symptoms and high mortality through chronic inflammation, tissue destruction, and serious infections. Despite numerous genomic ... ...

    Abstract Leukemic cutaneous T-cell lymphomas (L-CTCL) are lymphoproliferative disorders of skin-homing mature T-cells causing severe symptoms and high mortality through chronic inflammation, tissue destruction, and serious infections. Despite numerous genomic sequencing efforts, recurrent driver mutations have not been identified, but chromosomal losses and gains are frequent and dominant. We integrated genomic landscape analyses with innovative pharmacologic interference studies to identify key vulnerable nodes in L-CTCL. We detected copy number gains of loci containing the STAT3/5 oncogenes in 74% (n = 17/23) of L-CTCL, which correlated with the increased clonal T-cell count in the blood. Dual inhibition of STAT3/5 using small-molecule degraders and multi-kinase blockers abolished L-CTCL cell growth in vitro and ex vivo, whereby PAK kinase inhibition was specifically selective for L-CTCL patient cells carrying STAT3/5 gains. Importantly, the PAK inhibitor FRAx597 demonstrated encouraging anti-leukemic activity in vivo by inhibiting tumor growth and disease dissemination in intradermally xenografted mice. We conclude that STAT3/5 and PAK kinase interaction represents a new therapeutic node to be further explored in L-CTCL.
    MeSH term(s) Animals ; Mice ; p21-Activated Kinases ; Genomics ; Heterografts ; Lymphoma, T-Cell, Cutaneous/drug therapy
    Chemical Substances p21-Activated Kinases (EC 2.7.11.1)
    Language English
    Publishing date 2022-11-07
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2467145-9
    ISSN 1757-4684 ; 1757-4676
    ISSN (online) 1757-4684
    ISSN 1757-4676
    DOI 10.15252/emmm.202115200
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 6784: Show issues Location:
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