Potential involvement of IL-32 in cell-to-cell communication between macrophages and hepatoblastoma
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In brief
In brief
This study examines IL-32 expression in hepatoblastoma and its role in tumor-macrophage interactions. Findings suggest chemotherapy may induce IL-32 expression, which promotes protumor macrophage activation and potential chemoresistance through upregulation of immunosuppressive markers like PD-L1 and IDO-1.
Written by the GCMD Library team from the article.
Abstract
Purpose
This study investigated the expression of interleukin 32 (IL-32) in hepatoblastoma, the most common primary pediatric liver tumor, and its possible roles in tumorigenesis.
Methods
IL-32 expression was investigated in two hepatoblastoma cell lines (Hep G2 and HuH 6) in the steady state and after co-culture with macrophages by RNA-seq analysis and RT-qPCR, and after stimulation with chemotherapy. Cultured macrophages were stimulated by IL-32 isoforms followed by RT-qPCR and western blot analysis. IL-32 immunohistochemical staining (IHC) was performed using specimens from 21 hepatoblastoma patients. Clustering analysis was also performed using scRNA-seq data downloaded from Gene Expression Omnibus.
Results
The IL-32 gene is expressed by hepatoblastoma cell lines; expression is upregulated by paracrine cell–cell communication with macrophages, also by carboplatin and etoposide. IL-32 causes protumor activation of macrophages with upregulation of PD-L1, IDO-1, IL-6, and IL-10. In the patient pool, IHC was positive only in 48% of cases. However, in the downloaded dataset, IL-32 gene expression was negative.
Conclusion
IL-32 was detected in hepatoblastoma cell lines, but not in all hepatoblastoma patients. We hypothesized that stimulation such as chemotherapy might induce expression of IL-32, which might be a critical mediator of chemoresistance in hepatoblastoma through inducing protumor activation in macrophages.