Tertiary lymphoid structures critical for prognosis in endometrial cancer patients

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, Helen MacKay, Alexandra Leary, Naveena Singh, Ina M. Jürgenliemk-Schulz, Vincent T. H. B. M. Smit, Carien L. Creutzberg, Viktor H. Koelzer, Hans W. Nijman, Tjalling Bosse and Marco Bruyn
Additional contact information
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
Lisa Vermij: Leiden University Medical Center
Alicia Léon-Castillo: Leiden University Medical Center
Ricki T. Krog: 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
Hans W. Nijman: University Medical Center Groningen
Tjalling Bosse: Leiden University Medical Center
Marco Bruyn: University Medical Center Groningen

Nature Communications, 2022, vol. 13, issue 1, 1-10

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-29040-x

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