Pineda Sanjuan, SilviaLópez de Maturana, EvangelinaYu, KatharineRavoor, AkshayWood, InésMalats, NúriaSirota, MarinaNotarangelo, Luigi Daniele2024-01-222024-01-222021Pineda S, López de Maturana E, Yu K, Ravoor A, Wood I, Malats N and Sirota M (2021) Tumor-Infiltrating B- and T-Cell Repertoire in Pancreatic Cancer Associated With Host and Tumor Features. Front. Immunol. 12:730746.1664-322410.3389/fimmu.2021.730746https://hdl.handle.net/20.500.14352/94490Background: Infiltrating B and T cells have been observed in several tumor tissues, including pancreatic ductal adenocarcinoma (PDAC). The majority known PDAC risk factors point to a chronic inflammatory process leading to different forms of immunological infiltration. Understanding pancreatic tumor infiltration may lead to improved knowledge of this devastating disease. Methods: We extracted the immunoglobulins (IGs) and T cell receptors (TCRs) from RNA-sequencing of 144 PDAC from TCGA and 180 pancreatic normal tissue from GTEx. We used Shannon entropy to find differences in IG/TCR diversity. We performed a clonotype analysis considering the IG clone definition (same V and J segments, same CDR3 length, and 90% nucleotide identity between CDR3s) to study differences among the tumor samples. Finally, we performed an association analysis to find host and tumor factors associated with the IG/TCR. Results: PDAC presented a richer and more diverse IG and TCR infiltration than normal pancreatic tissue. A higher IG infiltration was present in heavy smokers and females and it was associated with better overall survival. In addition, specific IG clonotypes classified samples with better prognosis explaining 24% of the prognosis phenotypic variance. On the other hand, a larger TCR infiltration was present in patients with previous history of diabetes and was associated with lower nonantigen load. Conclusions: Our findings support PDAC subtyping according to its immune repertoire landscape with a potential impact on the understanding of the inflammatory basis of PDAC risk factors as well as the design of treatment options and prognosis monitoringengAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/journal articlehttps//doi.org/10.3389/fimmu.2021.730746https://www.frontiersin.org/articles/10.3389/fimmu.2021.730746/fullhttps://www.frontiersin.org/journals/immunologyopen access612.017519.2:57B-cell repertoireImmunoglobulinsT-cell repertoirePancreatic cancerTumor microenvironmentTumor infiltrationCompositional analysisInmunologíaBioinformática2412 Inmunología2404.01 Bioestadística