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.

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.

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.

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.

在多种肿瘤组织中观察到浸润的 B 和 T 细胞，包括胰腺导管腺癌 (PDAC)。大多数已知的 PDAC 风险因素都指向导致不同形式免疫浸润的慢性炎症过程。了解胰腺肿瘤浸润可能会提高对这种破坏性疾病的认识。

我们从来自 TCGA 的 144 个 PDAC 和来自 GTEx 的 180 个胰腺正常组织的 RNA 测序中提取了免疫球蛋白 (IG) 和 T 细胞受体 (TCR)。我们使用香农熵来发现 IG/TCR 多样性的差异。我们根据 IG 克隆定义（相同的 V 和 J 片段、相同的 CDR3 长度和 CDR3 之间的 90% 核苷酸同一性）进行了克隆型分析，以研究肿瘤样本之间的差异。最后，我们进行了关联分析以找到与 IG/TCR 相关的宿主和肿瘤因素。

PDAC 表现出比正常胰腺组织更丰富、更多样化的 IG 和 TCR 浸润。重度吸烟者和女性中存在更高的 IG 浸润，这与更好的总体生存率相关。此外，特定 IG 克隆型对具有更好预后的样本进行分类，解释了 24% 的预后表型变异。另一方面，既往有糖尿病病史的患者存在较大的 TCR 浸润，并且与较低的非抗原负荷相关。

我们的研究结果支持 PDAC 根据其免疫谱图进行亚型分型，这对理解 PDAC 危险因素的炎症基础以及治疗方案的设计和预后监测具有潜在影响。