Tertiary lymphoid structures critical for prognosis in endometrial cancer patients

TransPORTEC consortium, Nanda Horeweg, Hagma H Workel, Dominik Loiero, David N Church, Lisa Vermij, Alicia Léon-Castillo, Ricki T Krog, Stephanie M de 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 NijmanTjalling Bosse, Marco de Bruyn

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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 naive 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.

Tertiary lymphoid structures (TLS) are associated with a reduced risk of cancer recurrence and improved response to immune checkpoint blockade in several tumor types. Here the authors identify L1CAM as a marker for mature TLS and show that the presence of TLS is associated with favorable prognosis in patients with endometrial cancer from the PORTEC-3 trial.

Original languageEnglish
Article number1373
Number of pages10
JournalNature Communications
Volume13
Issue number1
DOIs
Publication statusPublished - 16-Mar-2022

Keywords

  • B-CELLS
  • IMMUNOTHERAPY
  • CLUSTERPROFILER
  • RESPONSES
  • SURVIVAL

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