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A macrophage-predominant immunosuppressive microenvironment and therapeutic vulnerabilities in advanced salivary gland cancer

Author

Listed:
  • Erika Zuljan

    (Berlin Institute of Health at Charité–Universitätsmedizin Berlin)

  • Benjamin Emde

    (Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin)

  • Iris Piwonski

    (Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin)

  • Ana Pestana

    (Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin
    a partnership between DKFZ and Charité - Universitätsmedizin Berlin)

  • Konrad Klinghammer

    (Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin
    a partnership between DKFZ and Charité - Universitätsmedizin Berlin
    BIH and MDC)

  • Andreas Mock

    (core center Heidelberg
    Ludwig-Maximilians-University Munich
    German Cancer Research Center (DKFZ)
    a partnership between DKFZ and Heidelberg University Hospital)

  • Peter Horak

    (core center Heidelberg
    German Cancer Research Center (DKFZ)
    a partnership between DKFZ and Heidelberg University Hospital)

  • Christoph Heining

    (and Helmholtz-Zentrum Dresden - Rossendorf (HZDR)
    TUD Dresden University of Technology
    partner site Dresden)

  • Frederick Klauschen

    (Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin
    a partnership between DKFZ and Charité - Universitätsmedizin Berlin
    Ludwig-Maximilians-University Munich
    partner site Munich)

  • Ina Pretzell

    (West German Cancer Center
    partner site Essen)

  • Melanie Boerries

    (University of Freiburg
    a partnership between DKFZ and Medical Center - University of Freiburg)

  • Christian H. Brandts

    (Hematology/Oncology & University Cancer Center Frankfurt (UCT)
    partner site Frankfurt)

  • Simon Kreutzfeldt

    (core center Heidelberg
    German Cancer Research Center (DKFZ)
    a partnership between DKFZ and Heidelberg University Hospital)

  • Maria-Veronica Teleanu

    (core center Heidelberg
    German Cancer Research Center (DKFZ)
    a partnership between DKFZ and Heidelberg University Hospital)

  • Daniel Hübschmann

    (core center Heidelberg
    German Cancer Research Center (DKFZ)
    a partnership between DKFZ and Heidelberg University Hospital)

  • Luc G. T. Morris

    (Memorial Sloan Kettering Cancer Center)

  • Max Heiland

    (BIH and MDC
    Humboldt-Universität zu Berlin)

  • Ulrich Keller

    (Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin
    a partnership between DKFZ and Charité - Universitätsmedizin Berlin
    BIH and MDC)

  • Thomas Conrad

    (Berlin Institute of Health at Charité - Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine in the Helmholtz Association)

  • Hanno Glimm

    (and Helmholtz-Zentrum Dresden - Rossendorf (HZDR)
    TUD Dresden University of Technology
    partner site Dresden)

  • Stefan Fröhling

    (core center Heidelberg
    German Cancer Research Center (DKFZ)
    a partnership between DKFZ and Heidelberg University Hospital
    Heidelberg University)

  • Sebastian Ochsenreither

    (Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin
    Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin
    a partnership between DKFZ and Charité - Universitätsmedizin Berlin
    BIH and MDC)

  • Ulrich Keilholz

    (Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin
    a partnership between DKFZ and Charité - Universitätsmedizin Berlin
    BIH and MDC)

  • Eric Blanc

    (Berlin Institute of Health at Charité–Universitätsmedizin Berlin)

  • Dieter Beule

    (Berlin Institute of Health at Charité–Universitätsmedizin Berlin)

  • Damian T. Rieke

    (Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin
    Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin
    a partnership between DKFZ and Charité - Universitätsmedizin Berlin
    BIH and MDC)

Abstract

Salivary gland cancers are rare, diverse malignancies characterized by poor response to immunotherapy. The tumor immune environment in these cancers remains poorly understood. To address this, we perform an integrative analysis of the tumor immune microenvironment in a large cohort of advanced salivary gland cancer samples. Most tumors exhibit low immune activity with limited immune cell infiltration. Inflammation is linked to higher tumor mutational burden in non-adenoid cystic carcinoma histologies. Subtype specific expression of immune checkpoints is identified with prominent expression of VTCN1 in luminal-like cells within adenoid cystic carcinoma. Macrophages with immunosuppressive properties dominate the immune microenvironment across subtypes. Responses to immunotherapy are limited and associated with a higher ratio of T-cells relative to macrophages in individual cases, warranting further investigation. Here, we show an immunosuppressive environment in salivary gland cancers and identify subtype-specific immune vulnerabilities that could inform tailored therapeutic strategies.

Suggested Citation

  • Erika Zuljan & Benjamin Emde & Iris Piwonski & Ana Pestana & Konrad Klinghammer & Andreas Mock & Peter Horak & Christoph Heining & Frederick Klauschen & Ina Pretzell & Melanie Boerries & Christian H. , 2025. "A macrophage-predominant immunosuppressive microenvironment and therapeutic vulnerabilities in advanced salivary gland cancer," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60421-0
    DOI: 10.1038/s41467-025-60421-0
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    References listed on IDEAS

    as
    1. Shashank J. Patel & Neville E. Sanjana & Rigel J. Kishton & Arash Eidizadeh & Suman K. Vodnala & Maggie Cam & Jared J. Gartner & Li Jia & Seth M. Steinberg & Tori N. Yamamoto & Anand S. Merchant & Gau, 2017. "Identification of essential genes for cancer immunotherapy," Nature, Nature, vol. 548(7669), pages 537-542, August.
    2. Kosuke Yoshihara & Maria Shahmoradgoli & Emmanuel Martínez & Rahulsimham Vegesna & Hoon Kim & Wandaliz Torres-Garcia & Victor Treviño & Hui Shen & Peter W. Laird & Douglas A. Levine & Scott L. Carter , 2013. "Inferring tumour purity and stromal and immune cell admixture from expression data," Nature Communications, Nature, vol. 4(1), pages 1-11, December.
    Full references (including those not matched with items on IDEAS)

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