%0 Journal Article
%A Pineda Sanjuan, Silvia
%A López de Maturana, Evangelina
%A Yu, Katharine
%A Ravoor, Akshay
%A Wood, Inés
%A Malats, Núria
%A Sirota, Marina
%T Tumor-infiltrating b-and T-cell repertoire in pancreatic cancer associated with host and tumor features
%D 2021
%@ 1664-3224
%U https://hdl.handle.net/20.500.14352/94490
%X Background: 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 monitoring
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