Journal
NEOPLASIA
Volume 28, Issue -, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neo.2022.100789
Keywords
Pancreas cancer; Bioinformatics; Immunology; Immune checkpoint; Survival
Categories
Funding
- National Human Genome Research Institute [T32 HG0008958]
- National Cancer Institute of the National Institutes of Health [1U01DK108320]
- National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health [1U01DK108320]
Ask authors/readers for more resources
Interleukin-1 (IL-1) plays a crucial role in pancreatic ductal adenocarcinoma (PDAC) and is associated with immune checkpoints, immune cell types, and patient 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 < 0.001), IL1RN ( p < 0.001), IL1R2 ( p < 0.001), and IL1RAP ( p = 0.006) were markedly increased in PDAC tumor tissue compared to benign pancreatic tissue. Furthermore, expression of IL1A, IL1B and IL1R1 were positively correlated with gene expression of immune checkpoints PVR, CD274, CD47, CD80, and HLA-A/B/C ( p < 0.001). IL1B and IL1R1 were correlated to expression of PDCD1, CD86, CTLA4 and IDO1 ( < 0.001). Low expression of IL1RN ( p = 0.020), IL1R2 ( p = 0.015), and IL1RAP ( p = 0.003) and high expression of IL1B ( p = 0.031) were correlated with increased patient survival. At the protein level, IL-1 beta was correlated with increased peripheral central memory CD4+ and CD8+ T-cells as well as decreased Th2 cells. These findings suggest that the IL-1 axis plays a complex and pivotal role in the host immune response to PDAC.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available