Tumor-Infiltrating B- and T-Cell Repertoire in Pancreatic Cancer Associated With Host and Tumor Features

Abstract

BackgroundInfiltrating 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.MethodsWe 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.ResultsPDAC 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.ConclusionsOur 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.

Identification of a Disulfidptosis-related gene associated with the prognosis of pancreatic cancer

“…In addition, immune in ltration also signi cantly affects the development of cancer (30). Pancreatic cancer has been con rmed to be closely related to the in ltration of T cells and B lymphocytes in immune cells (31) and is signi cantly higher than normal pancreatic tissue, which is consistent with our research results. pancreatic cancer tissue has a high level of in ltration of CD8T cells, regulatory T cells, B cells, and other immune cells (32).…”

Prognostic Stratification Based on HIF-1 Signaling for Evaluating Hypoxic Status and Immune Infiltration in Pancreatic Ductal Adenocarcinomas

“…Interestingly, using a genetic animal model, Lee et al demonstrated accumulation of HIF-1α in early pancreatic neoplasia but HIF-1α deletion accelerates PDAC initiation by increasing B cell infiltration, suggesting the pro-neoplastic effect of B cells ( 79 ). However, the role of B cells in anti-tumor immunity is still controversial ( 80 , 81 ). Therefore, further studies are needed to clarify the role of B cell immunity in human PDAC and its interaction with HIF-1.…”

Integrated analysis of tertiary lymphoid structures in relation to tumor-infiltrating lymphocytes and patient survival in pancreatic ductal adenocarcinoma

“…In previous studies [42,43], the smoking history has been associated with higher tumor-infiltrating immune cells in breast and lung cancer patients. In PDAC, Pineda et al [44] showed that smoking might increase the incidence of somatic mutations, generate neoantigens, and cause an amplified immunogenicity. Antitumor immune responses induced by smoking might promote TLS development in PDAC.…”