single cell mRNA sequencing of B cells from human endometrial cancers

Emerging data indicate that B-cells play a key role in cancer suppression, particularly when aggregated in tertiary lymphoid-like structures (TLS). Here, we used single-cell and bulk RNA sequencing of endometrial cancers (ECs) and found L1-cell adhesion molecule L1CAM to be significantly associated with TLS. Immunohistochemical (IHC) expression of L1CAM was restricted to the germinal centre (GC) of mature TLS, where it co-localised with follicular dendritic cell (FDC) marker CD21. Tumours surrounded by L1CAM-positive TLS were identified across all molecular EC subgroups, but enriched in mismatch repair deficient (MMRd) and polymerase-epsilon mutant (POLEmut) EC, especially when TP53 mutations were also present. Importantly, L1CAM-positive TLS appeared an independent favourable predictor of EC recurrence and death, and significantly improved the current prognostic molecular EC classification based on clinicopathological and molecular factors. Our data suggest a pivotal role of TLS in predicting outcome of EC patients, and establishes L1CAM as a simple and widely available biomarker of TLS in clinical care. 1513 single B cells from 6 patients