Tertiary lymphoid structures critical for prognosis in endometrial cancer patients

• DOI: 10.1038/s41467-022-29040-x
• Publication Date: 2022-03-16T11:03:55Z
• Authors: 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. Jürgenliem...; Vincent T. H. B. ...; Carien L. Creutzberg; Viktor H. Koelzer; Hans W. Nijman; Tjalling Bosse; Marco de Bruyn; ; Nanda Horeweg; David N. Church; Stephanie M. de Boer; Remi A. Nout; Melanie E. Powell; Linda R. Mileshkin; Helen MacKay; Alexandra Leary; Naveena Singh; Carien L. Creutzberg; Hans W. Nijman; Tjalling Bosse; Marco de Bruyn
• Keywords: 0301 basic medicine; CLUSTERPROFILER; Science; Q; 610; Neural Cell Adhesion Molecule L1; Germinal Center; Immunohistochemistry; Article; Endometrial Neoplasms; 03 medical and health sciences; Tertiary Lymphoid Structures; SDG 3 - Good Health and Well-being; B-CELLS; SURVIVAL; Humans; Female; IMMUNOTHERAPY; RESPONSES

B-cells play a key role in cancer suppression, particularly when aggregated tertiary lymphoid structures (TLS). Here, we investigate the of and TLS endometrial (EC). Single cell RNA-sequencing shows presence naïve B-cells, cycling/germinal center antibody-secreting cells. Differential gene expression analysis association with L1CAM overexpression. Immunohistochemistry co-immunofluorescence show mature TLS, independent tumor. Using as marker, 378 411 molecularly classified ECs from PORTEC-3 biobank are evaluated, found 19%. expressing most common mismatch-repair deficient (29/127, 23%) polymerase-epsilon mutant EC (24/47, 51%). Multivariable Cox regression strong favorable prognostic impact clinicopathological molecular factors. Our data suggests pivotal outcome patients, establishes simple biomarker.