The interleukin-1 axis and the tumor immune microenvironment in pancreatic ductal adenocarcinoma

•Distinct changes in gene expression of the IL-1 axis are found in PDAC.•IL-1 axis expression is correlated with changes in immune checkpoint proteins.•Changes in the IL-1 axis impact the tumor immune milieu.•Low tumor expression of IL1B is associated with decreased overall survival. Interleukin-1 (...

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Published in:Neoplasia (New York, N.Y.) N.Y.), 2022-06, Vol.28, p.100789, Article 100789
Main Authors: Herremans, Kelly M., Szymkiewicz, Dominique D., Riner, Andrea N., Bohan, Riley P., Tushoski, Gerik W., Davidson, Aaron M., Lou, XiangYang, Leong, Man Chong, Dean, Bayli DiVita, Gerber, Michael, Underwood, Patrick W., Han, Song, Hughes, Steven J.
Format: Article
Language:English
Subjects:
Bioinformatics
Carcinoma, Pancreatic Ductal - genetics
Carcinoma, Pancreatic Ductal - pathology
CD8-Positive T-Lymphocytes
Humans
Immune checkpoint
Immunology
Original article
Pancreas cancer
Pancreatic Neoplasms
Pancreatic Neoplasms - genetics
Survival
Tumor Microenvironment - genetics
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Summary:•Distinct changes in gene expression of the IL-1 axis are found in PDAC.•IL-1 axis expression is correlated with changes in immune checkpoint proteins.•Changes in the IL-1 axis impact the tumor immune milieu.•Low tumor expression of IL1B is associated with decreased overall survival. Interleukin-1 (IL-1) plays a key role in carcinogenesis and several IL-1-targeted therapeutics are under investigation for the treatment of pancreatic ductal adenocarcinoma (PDAC). We sought to broaden our understanding of how the family of IL-1 ligands and receptors impact the tumor immune landscape and patient survival in PDAC. Gene expression data and DNA methylation data for IL1A, IL1B, IL1RN, IL1R1, IL1R2, and IL1RAP was attained from The Cancer Genome Atlas (TCGA) database and cross validated using the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database. Immune cell-type abundance was estimated using CIBERSORTx. Further confirmatory soluble protein analysis and peripheral blood immunophenotyping were performed on available tissue samples from our institution. 169 PDAC patients and 50 benign pancreatic TCGA-based samples were analyzed. IL1A (p 
ISSN:1476-5586
1522-8002
1476-5586
DOI:10.1016/j.neo.2022.100789