TY - JOUR
T1 - Tertiary lymphoid structures critical for prognosis in endometrial cancer patients
AU - TransPORTEC consortium
AU - Horeweg, Nanda
AU - Workel, Hagma H.
AU - Loiero, Dominik
AU - Church, David N.
AU - Vermij, Lisa
AU - Léon-Castillo, Alicia
AU - Krog, Ricki T.
AU - de Boer, Stephanie M.
AU - Nout, Remi A.
AU - Powell, Melanie E.
AU - Mileshkin, Linda R.
AU - MacKay, Helen
AU - Leary, Alexandra
AU - Singh, Naveena
AU - Jürgenliemk-Schulz, Ina M.
AU - Smit, Vincent T.H.B.M.
AU - Creutzberg, Carien L.
AU - Koelzer, Viktor H.
AU - Nijman, Hans W.
AU - Bosse, Tjalling
AU - de Bruyn, Marco
AU - Horeweg, Nanda
AU - Church, David N.
AU - de Boer, Stephanie M.
AU - Nout, Remi A.
AU - Powell, Melanie E.
AU - Leary, Alexandra
AU - Singh, Naveena
AU - Creutzberg, Carien L.
AU - Nijman, Hans W.
AU - Bosse, Tjalling
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12/1
Y1 - 2022/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85126703650&partnerID=8YFLogxK
U2 - 10.1038/s41467-022-29040-x
DO - 10.1038/s41467-022-29040-x
M3 - Article
C2 - 35296668
AN - SCOPUS:85126703650
SN - 2041-1723
VL - 13
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1373
ER -