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Lack of SMARCB1 expression characterizes a subset of human and murine peripheral T-cell lymphomas

Author

Listed:
  • Anja Fischer

    (Ulm University Medical Center)

  • Thomas K. Albert

    (University Children’s Hospital Münster)

  • Natalia Moreno

    (University Children’s Hospital Münster)

  • Marta Interlandi

    (University Children’s Hospital Münster
    University of Münster)

  • Jana Mormann

    (University Children’s Hospital Münster)

  • Selina Glaser

    (Ulm University Medical Center)

  • Paurnima Patil

    (Ulm University Medical Center)

  • Flavia W. Faria

    (University Children’s Hospital Münster)

  • Mathis Richter

    (University of Münster)

  • Archana Verma

    (University Children’s Hospital Münster)

  • Sebastian T. Balbach

    (University Children’s Hospital Münster)

  • Rabea Wagener

    (Ulm University Medical Center)

  • Susanne Bens

    (Ulm University Medical Center)

  • Sonja Dahlum

    (Ulm University Medical Center)

  • Carolin Göbel

    (Eppendorf (UKE)
    Research Institute Children’s Cancer Center)

  • Daniel Münter

    (University Children’s Hospital Münster)

  • Clara Inserte

    (University of Münster)

  • Monika Graf

    (University Children’s Hospital Münster)

  • Eva Kremer

    (University Children’s Hospital Münster)

  • Viktoria Melcher

    (University Children’s Hospital Münster)

  • Gioia Stefano

    (Careggi University Hospital)

  • Raffaella Santi

    (Careggi University Hospital)

  • Alexander Chan

    (Memorial Sloan Kettering Cancer Center)

  • Ahmet Dogan

    (Memorial Sloan Kettering Cancer Center)

  • Jonathan Bush

    (British Columbia Children’s Hospital and Women’s Hospital and Health Center)

  • Martin Hasselblatt

    (University Hospital Münster)

  • Sylvia Cheng

    (University of British Columbia)

  • Signe Spetalen

    (Oslo University Hospital
    University of Oslo)

  • Alexander Fosså

    (Oslo University Hospital-Norwegian Radium Hospital)

  • Wolfgang Hartmann

    (Gebäude D17)

  • Heidi Herbrüggen

    (University Children’s Hospital Münster)

  • Stella Robert

    (University Hospital Münster)

  • Florian Oyen

    (Eppendorf (UKE))

  • Martin Dugas

    (University of Münster
    Heidelberg University Hospital)

  • Carolin Walter

    (University of Münster)

  • Sarah Sandmann

    (University of Münster)

  • Julian Varghese

    (University of Münster)

  • Claudia Rossig

    (University Children’s Hospital Münster)

  • Ulrich Schüller

    (Eppendorf (UKE)
    Research Institute Children’s Cancer Center
    University Medical Center Hamburg-Eppendorf (UKE))

  • Alexandar Tzankov

    (University Hospital Basel)

  • Martin B. Pedersen

    (Aarhus University Hospital)

  • Francesco A. d’Amore

    (Aarhus University Hospital
    Aarhus University)

  • Karin Mellgren

    (The Queen Silvia Children’s Hospital)

  • Udo Kontny

    (RWTH Aachen University Hospital)

  • Venkatesh Kancherla

    (Lausanne University Hospital)

  • Luis Veloza

    (Lausanne University Hospital)

  • Edoardo Missiaglia

    (Lausanne University Hospital)

  • Virginie Fataccioli

    (Université Paris-Est
    Université Paris Est Créteil)

  • Philippe Gaulard

    (Université Paris Est Créteil)

  • Birgit Burkhardt

    (University Children’s Hospital Münster)

  • Oliver Soehnlein

    (University of Münster)

  • Wolfram Klapper

    (University Hospital Schleswig-Holstein)

  • Laurence Leval

    (Lausanne University Hospital)

  • Reiner Siebert

    (Ulm University Medical Center)

  • Kornelius Kerl

    (University Children’s Hospital Münster)

Abstract

Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous group of malignancies with poor outcome. Here, we identify a subgroup, PTCL-NOSSMARCB1-, which is characterized by the lack of the SMARCB1 protein and occurs more frequently in young patients. Human and murine PTCL-NOSSMARCB1- show similar DNA methylation profiles, with hypermethylation of T-cell-related genes and hypomethylation of genes involved in myeloid development. Single-cell analyses of human and murine tumors revealed a rich and complex network of interactions between tumor cells and an immunosuppressive and exhausted tumor microenvironment (TME). In a drug screen, we identified histone deacetylase inhibitors (HDACi) as a class of drugs effective against PTCL-NOSSmarcb1-. In vivo treatment of mouse tumors with SAHA, a pan-HDACi, triggered remodeling of the TME, promoting replenishment of lymphoid compartments and reversal of the exhaustion phenotype. These results provide a rationale for further exploration of HDACi combination therapies targeting PTCL-NOSSMARCB1- within the TME.

Suggested Citation

  • Anja Fischer & Thomas K. Albert & Natalia Moreno & Marta Interlandi & Jana Mormann & Selina Glaser & Paurnima Patil & Flavia W. Faria & Mathis Richter & Archana Verma & Sebastian T. Balbach & Rabea Wa, 2024. "Lack of SMARCB1 expression characterizes a subset of human and murine peripheral T-cell lymphomas," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52826-0
    DOI: 10.1038/s41467-024-52826-0
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    References listed on IDEAS

    as
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