Interleukin-37 (IL-37) is a relatively new
IL-1 family
cytokine that, due to its immunoregulatory properties, has lately gained increasing attention in basic and translational biomedical research. Emerging evidence supports the implication of this
protein in any human disorder in which immune homeostasis is compromised, including
cancer. The aim of this study was to explore the prognostic and/or diagnostic potential of IL-37 and its receptor SIGIRR (single
immunoglobulin IL-1-related receptor) in human
tumors. We utilized a series of bioinformatics tools and -omics datasets to unravel possible associations of IL-37 and SIGIRR expression levels and genetic aberrations with
tumor development, histopathological parameters, distribution of
tumor-infiltrating immune cells, and survival rates of patients. Our data revealed that amongst the 17 human
malignancies investigated, IL-37 exhibits higher expression levels in
tumors of
lung adenocarcinoma (LUAD). Moreover, the expression profiles of IL-37 and SIGIRR are associated with LUAD development and
tumor stage, whereas their high
mRNA levels are favorable prognostic factors for the overall survival of patients. What is more, IL-37 correlates positively with a LUAD-associated transcriptomic signature, and its
nucleotide changes and expression levels are linked with distinct infiltration patterns of certain cell subsets known to control LUAD anti-
tumor immune responses. Our data indicate the potential value of IL-37 and its receptor SIGIRR to serve as
biomarkers and/or immune-checkpoint therapeutic targets for LUAD patients. Further, the data highlight the urgent need for further exploration of this
cytokine and the underlying pathogenetic mechanisms to fully elucidate its implication in LUAD development and progression.