Interleukin 32 expression in human melanoma.

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Proinflammatory cytokines are present in the melanoma tumor microenvironment.
• Interleukin 32 (IL32) is produced by immune cells and a subset of melanoma cells.
• Understanding IL32 biology in human melanoma is crucial.

Purpose of the Study:

• To investigate the biology of IL32 in human melanoma.
• To analyze gene expression patterns associated with IL32.
• To evaluate the impact of TNFα and IFNγ on IL32 expression and melanoma cell dedifferentiation.

Main Methods:

• Analysis of RNA sequencing data from human melanoma cell lines and tumors (The Cancer Genome Atlas).
• In vitro experiments assessing the effect of TNFα and IFNγ on IL32 expression and dedifferentiation.
• Cloning of the IL32 gene's 5' upstream region to study transcriptional regulation using a luciferase reporter vector.

Main Results:

• IL32 expression is prevalent in melanoma cell lines and correlates with a dedifferentiation signature (high AXL/low MITF).
• TNFα and IFNγ induce IL32 expression (isoforms α, β, γ) in differentiated melanoma cells.
• Cis-acting elements in the IL32 5' upstream region regulate gene expression.
• Tumor microenvironment IL32 expression correlates with T cell infiltration and the dedifferentiated signature.

Conclusions:

• IL32 expression in melanoma is inducible by TNFα/IFNγ and associated with a treatment-resistant, dedifferentiated phenotype.
• Both constitutive and induced IL32 expression are partly regulated by cis-acting sequences in the 5' upstream region.