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Tertiary lymphoid structure (TLS) is an organized cluster of immune cells in nonlymphoid tissues that have prognostic potential in patients treated with immunotherapies. Manual TLS annotation is error-prone and labor-intensive due to histomorphological diversity. Gene signatures have been developed as potential proxies for TLS. This study assesses the association of TLS between gene signatures and pathological phenotyping in pancreatic ductal adenocarcinoma (PDAC).

Enrichment scores for 6 published TLS gene signatures^1–3 were calculated using PDAC tumor RNA sequencing data (n=180) from TCGA (The Cancer Genome Atlas). Three pathologists evaluated H&E-stained images (n=205) to determine TLS and germinal center (GC) presence. Analysis included 158 images with definitive pathology classifications. Using the slideflow⁴ framework, we applied a multiple-instance …