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Tertiary lymphoid structures critical for prognosis in endometrial cancer patients

Author

Listed:
  • Nanda Horeweg

    (Leiden University Medical Center)

  • Hagma H. Workel

    (University Medical Center Groningen)

  • Dominik Loiero

    (University Hospital Zurich, University of Zurich)

  • David N. Church

    (University of Oxford
    Oxford University Hospitals NHS Foundation Trust)

  • Lisa Vermij

    (Leiden University Medical Center)

  • Alicia Léon-Castillo

    (Leiden University Medical Center)

  • Ricki T. Krog

    (Leiden University Medical Center
    Leiden University Medical Center)

  • Stephanie M. Boer

    (Leiden University Medical Center)

  • Remi A. Nout

    (Erasmus MC Cancer Institute)

  • Melanie E. Powell

    (Barts Health NHS Trust)

  • Linda R. Mileshkin

    (Peter MacCallum Cancer Centre)

  • Helen MacKay

    (Sunnybrook Odette Cancer Centre)

  • Alexandra Leary

    (Gustave Roussy)

  • Naveena Singh

    (Barts Health NHS Trust)

  • Ina M. Jürgenliemk-Schulz

    (University Medical Center Utrecht)

  • Vincent T. H. B. M. Smit

    (Leiden University Medical Center)

  • Carien L. Creutzberg

    (Leiden University Medical Center)

  • Viktor H. Koelzer

    (University Hospital Zurich, University of Zurich
    University of Oxford)

  • Hans W. Nijman

    (University Medical Center Groningen)

  • Tjalling Bosse

    (Leiden University Medical Center)

  • Marco Bruyn

    (University Medical Center Groningen)

Abstract

B-cells play a key role in cancer suppression, particularly when aggregated in tertiary lymphoid structures (TLS). Here, we investigate the role of B-cells and TLS in endometrial cancer (EC). Single cell RNA-sequencing of B-cells shows presence of naïve B-cells, cycling/germinal center B-cells and antibody-secreting cells. Differential gene expression analysis shows association of TLS with L1CAM overexpression. Immunohistochemistry and co-immunofluorescence show L1CAM expression in mature TLS, independent of L1CAM expression in the tumor. Using L1CAM as a marker, 378 of the 411 molecularly classified ECs from the PORTEC-3 biobank are evaluated, TLS are found in 19%. L1CAM expressing TLS are most common in mismatch-repair deficient (29/127, 23%) and polymerase-epsilon mutant EC (24/47, 51%). Multivariable Cox regression analysis shows strong favorable prognostic impact of TLS, independent of clinicopathological and molecular factors. Our data suggests a pivotal role of TLS in outcome of EC patients, and establishes L1CAM as a simple biomarker.

Suggested Citation

  • Nanda Horeweg & Hagma H. Workel & Dominik Loiero & David N. Church & Lisa Vermij & Alicia Léon-Castillo & Ricki T. Krog & Stephanie M. Boer & Remi A. Nout & Melanie E. Powell & Linda R. Mileshkin & He, 2022. "Tertiary lymphoid structures critical for prognosis in endometrial cancer patients," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29040-x
    DOI: 10.1038/s41467-022-29040-x
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    References listed on IDEAS

    as
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    3. Rita Cabrita & Martin Lauss & Adriana Sanna & Marco Donia & Mathilde Skaarup Larsen & Shamik Mitra & Iva Johansson & Bengt Phung & Katja Harbst & Johan Vallon-Christersson & Alison Schoiack & Kristina, 2020. "Tertiary lymphoid structures improve immunotherapy and survival in melanoma," Nature, Nature, vol. 577(7791), pages 561-565, January.
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    Cited by:

    1. Benjamin L. Walker & Qing Nie, 2023. "NeST: nested hierarchical structure identification in spatial transcriptomic data," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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