Tertiary lymphoid structures critical for prognosis in endometrial cancer patients
- Author(s)
- Horeweg, N; Workel, HH; Loiero, D; Church, DN; Vermij, L; Leon-Castillo, A; Krog, RT; de Boer, SM; Nout, RA; Powell, ME; Mileshkin, LR; Mackay, H; Leary, A; Singh, N; Jurgenliemk-Schulz, IM; Smit, VTHBM; Creutzberg, CL; Koelzer, VH; Nijman, HW; Bosse, T; de Bruyn, M; TransPORTEC Consortium;
- Journal Title
- Nature Communications
- Publication Type
- Research article
- 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.
- Keywords
- *Endometrial Neoplasms/pathology; Female; Germinal Center/metabolism; Humans; Immunohistochemistry; *Neural Cell Adhesion Molecule L1; *Tertiary Lymphoid Structures/genetics
- Department(s)
- Medical Oncology
- PubMed ID
- 35296668
- Publisher's Version
- https://doi.org/10.1038/s41467-022-29040-x
- Open Access at Publisher's Site
https://doi.org/10.1038/s41467-022-29040-x- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2024-11-08 06:56:19
Last Modified: 2024-11-08 06:56:45