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Tertiary lymphoid structures critical for prognosis in endometrial cancer patients

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.Tertiary lymphoid structures (TLS) are associated with a reduced risk of cancer recurrence and improved response to immune checkpoint blockade in several tumor types. Here the authors identify L1CAM as a marker for mature TLS and show that the presence of TLS is associated with favorable prognosis in patients with endometrial cancer from the PORTEC-3 trial.Biological, physical and clinical aspects of cancer treatment with ionising radiatio
Publication status:
Published
Peer review status:
Peer reviewed

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Role:
Author
ORCID:
0009-0006-7910-0099
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Role:
Author
ORCID:
0000-0002-0452-0068
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Institution:
University of Oxford
Role:
Author
ORCID:
0000-0002-4617-962X
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Role:
Author
ORCID:
0000-0003-4687-5550


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Funder identifier:
10.13039/100004440
Grant:
203141/Z/16/Z
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Funder identifier:
10.13039/501100008307
Grant:
F-87701-41-01
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Funder identifier:
10.13039/501100000289
Grant:
C26642/A27963
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Funder identifier:
10.13039/501100004622
Grant:
KWF-2021-13400


Publisher:
Nature Research
Journal:
Nature Communications More from this journal
Volume:
13
Issue:
1
Pages:
1373-1373
Article number:
1373
Publication date:
2022-03-16
DOI:
EISSN:
2041-1723
ISSN:
2041-1723


Language:
English
Keywords:
Pubs id:
1243149
Local pid:
pubs:1243149
Source identifiers:
W4220818710
Deposit date:
2026-04-10
ARK identifier:
This ORA record was generated from metadata provided by an external service. It has not been edited by the ORA Team.

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