Tertiary lymphoid structures (TLS) have recently been shown to be predictive of survival in pancreatic adenocarcinoma (PDAC). This project aims to quantify and subtype TLS in three PDAC cohorts spanning over 600 patients. These findings will then be associated with clinical metadata, genomic mutations and transcriptional subtypes. The successful candidate will benchmark existing TLS identification methods and compare these to recently developed foundation models. Upon identification, we will attempt to stratify TLS into distinct subtypes based on the embeddings produced by foundation models. We will then attempt to identify whether these subtypes are driven by TLS specific aspects such as lymphocyte morphology or the surrounding environment such as the composition of the stroma or distance to the closest tumor. Finally, we will benchmark the extent to which these subtypes recapitulate transcriptional TLS subtypes we have already identified using spatial sequencing technologies. Upon creation of a robust TLS subtyping method, we will run it over slides from over 600 deeply phenotyped patients and associate the presence and TLS subtype with patient survival, genomic mutations and copy number aberrations as well as known transcriptional subtypes. Overall, this will be the most in-depth characterization of TLS’ in PDAC to date.