Tertiary lymphoid structures critical for prognosis in endometrial cancer patients.
Nanda HorewegHagma H WorkelDominik LoieroDavid N ChurchLisa VermijAlicia Léon-CastilloRicki T KrogStephanie M de BoerRemi A NoutMelanie E PowellLinda R MileshkinHelen MacKayAlexandra LearyNaveena SinghIna M Jürgenliemk-SchulzVincent T H B M SmitCarien L CreutzbergViktor Hendrik KoelzerHans W NijmanTjalling BosseMarco de Bruynnull nullPublished in: Nature communications (2022)
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.
Keyphrases
- endometrial cancer
- end stage renal disease
- single cell
- ejection fraction
- newly diagnosed
- poor prognosis
- chronic kidney disease
- prognostic factors
- peritoneal dialysis
- patient reported outcomes
- squamous cell carcinoma
- gene expression
- high resolution
- cell proliferation
- papillary thyroid
- long non coding rna
- binding protein
- high intensity
- electronic health record
- oxidative stress
- single molecule
- signaling pathway
- patient reported
- childhood cancer
- endoplasmic reticulum stress