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Updated: Jan 26, 2026
Generation of Induced Pluripotent Stem Cells from Human Melanoma Tumor-infiltrating Lymphocytes
Published on: November 11, 2016
Interleukin 32 expression in human melanoma
Helicia Paz1, Jennifer Tsoi2,3, Anusha Kalbasi1,4,5
1Department of Surgery, University of California, Los Angeles, 10833 Le Conte Ave, Los Angeles, CA, 90095, USA.
Background:
Various proinflammatory cytokines can be detected within the melanoma tumor microenvironment. Interleukin 32 (IL32) is produced by T cells, NK cells and monocytes/macrophages, but also by a subset of melanoma cells. We sought to better understand the biology of IL32 in human melanoma.
Methods:
We analyzed RNA sequencing data from 53 in-house established human melanoma cell lines and 479 melanoma tumors from The Cancer Genome Atlas dataset. We evaluated global gene expression patterns associated with IL32 expression. We also evaluated the impact of proinflammatory molecules TNFα and IFNγ on IL32 expression and dedifferentiation in melanoma cell lines in vitro. In order to study the transcriptional regulation of IL32 in these cell lines, we cloned up to 10.5 kb of the 5' upstream region of the human IL32 gene into a luciferase reporter vector.
Results:
A significant proportion of established human melanoma cell lines express IL32, with its expression being highly correlated with a dedifferentiation genetic signature (high AXL/low MITF). Non IL32-expressing differentiated melanoma cell lines exposed to TNFα or IFNγ can be induced to express the three predominant isoforms (α, β, γ) of IL32. Cis-acting elements within this 5' upstream region of the human IL32 gene appear to govern both induced and constitutive gene expression. In the tumor microenvironment, IL32 expression is highly correlated with genes related to T cell infiltration, and also positively correlates with high AXL/low MITF dedifferentiated gene signature.
Conclusions:
Expression of IL32 in human melanoma can be induced by TNFα or IFNγ and correlates with a treatment-resistant dedifferentiated genetic signature. Constitutive and induced expression are regulated, in part, by cis-acting sequences within the 5' upstream region.
Insights
Interleukin 32 (IL32) expression in melanoma is induced by inflammatory cytokines and linked to a dedifferentiated, treatment-resistant state. Its regulation involves upstream gene sequences and T cell infiltration markers.
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.
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