Tertiary lymphoid structures critical for prognosis in endometrial cancer patients.
Horeweg N., Workel HH., Loiero D., Church DN., Vermij L., Léon-Castillo A., Krog RT., de Boer SM., Nout RA., Powell ME., Mileshkin LR., MacKay H., Leary A., Singh N., Jürgenliemk-Schulz IM., Smit VTHBM., Creutzberg CL., Koelzer VH., Nijman HW., Bosse T., de Bruyn M., TransPORTEC consortium None.
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.