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ObjectiveTo better understand the immune microenvironment of pancreatic ductal adenocarcinomas (PDACs), here we explored the relevance of T and B cell compartmentalisation into tertiary lymphoid structures (TLSs) for the generation of local antitumour immunity.DesignWe characterised the functional states and spatial organisation of PDAC-infiltrating T and B cells using single-cell RNA sequencing (scRNA-seq), flow cytometry, multicolour immunofluorescence, gene expression profiling of microdissected TLSs, as well as in vitro assays. In addition, we performed a pan-cancer analysis of tumour-infiltrating T cells using scRNA-seq and sc T cell receptor sequencing datasets from eight cancer types. To evaluate the clinical relevance of our findings, we used PDAC bulk RNA-seq data from The Cancer Genome Atlas and the PRINCE chemoimmunotherapy trial.ResultsWe found that a subset of PDACs harbours fully developed TLSs where B cells proliferate and differentiate into plasma cells. These mature TLSs also support T cell activity and are enriched with tumour-reactive T cells. Importantly, we showed that chronically activated, tumour-reactive T cells exposed to fibroblast-derived TGF-β may act as TLS organisers by producing the B cell chemoattractant CXCL13. Identification of highly similar subsets of clonally expandedCXCL13+tumour-infiltrating T cells across multiple cancer types further indicated a conserved link between tumour-antigen recognition and the allocation of B cells within sheltered hubs in the tumour microenvironment. Finally, we showed that the expression of a gene signature reflecting mature TLSs was enriched in pretreatment biopsies from PDAC patients with longer survival after receiving different chemoimmunotherapy regimens.ConclusionWe provided a framework for understanding the biological role of PDAC-associated TLSs and revealed their potential to guide the selection of patients for future immunotherapy trials.

Background: The delay in gastric emptying is the second most frequent complication after duodenopancreatectomy with pyloric preservation, that increases hospitalization time and hospital costs. Aim: To identify factors that contribute to the appearance the delay in this surgical procedure. Method: Ninety-five patients were submitted to duodenopancreatectomy with pyloric preservation. After retrospective analysis of the medical records, it was observed that 60 had prolonged hospitalization due to complications. Thus, univariate and multivariate logistic regression were used to analyze predictors of delayed gastric emptying. Results: Delay was present in 65% (n=39) and pancreatic fistula in 38.3% (n=23). Univariate analysis revealed that the presence of pancreatic complications (pancreatic fistula, p=0.01), other intracavitary complications with the appearance of abdominal collections (p=0.03) and hypoalbuminemia (p=0.06) were responsible, also confirmed by the multivariate analysis. In those who presented delay without a determined cause, it was observed that high levels of total bilirubin (p=0.01) and direct bilirubin (p=0.01) could be related to it. Conclusion: The delay in gastric emptying in patients undergoing duodenopancreatectomy with pyloric preservation is due to intracavitary complications.

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