Tertiary lymphoid structures critical for prognosis in endometrial cancer patients.

Autor: Horeweg N; Department of Radiation Oncology, Leiden University Medical Center, Leiden, the Netherlands. n.horeweg@lumc.nl., Workel HH; Department of Gynaecologic Oncology, University Medical Center Groningen, Groningen, the Netherlands., Loiero D; Department of Pathology and Molecular Pathology, University Hospital Zurich, University of Zurich, Zurich, Switzerland., Church DN; Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.; Oxford NIHR Comprehensive Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom., Vermij L; Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands., Léon-Castillo A; Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands., Krog RT; Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.; Department Surgery, Leiden University Medical Center, Leiden, the Netherlands., de Boer SM; Department of Radiation Oncology, Leiden University Medical Center, Leiden, the Netherlands., Nout RA; Department of Radiotherapy, Erasmus MC Cancer Institute, Rotterdam, the Netherlands., Powell ME; Department of Clinical Oncology, Barts Health NHS Trust, London, United Kingdom., Mileshkin LR; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia., MacKay H; Division of Medical Oncology and Hematology, Sunnybrook Odette Cancer Centre, Toronto, ON, Canada., Leary A; Department of Medical Oncology, Gustave Roussy, Villejuif, France., Singh N; Department of Pathology, Barts Health NHS Trust, London, United Kingdom., Jürgenliemk-Schulz IM; Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, the Netherlands., Smit VTHBM; Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands., Creutzberg CL; Department of Radiation Oncology, Leiden University Medical Center, Leiden, the Netherlands., Koelzer VH; Department of Pathology and Molecular Pathology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.; Department of Oncology and Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Nijman HW; Department of Gynaecologic Oncology, University Medical Center Groningen, Groningen, the Netherlands., Bosse T; Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands., de Bruyn M; Department of Gynaecologic Oncology, University Medical Center Groningen, Groningen, the Netherlands.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Mar 16; Vol. 13 (1), pp. 1373. Date of Electronic Publication: 2022 Mar 16.
DOI: 10.1038/s41467-022-29040-x
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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