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Updated: Aug 8, 2025
Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
Published on: January 7, 2019
IL-32 is induced by activation of toll-like receptors in multiple myeloma cells
Kristin Roseth Aass1, Synne Stokke Tryggestad1, Robin Mjelle1,2,3
1Centre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Abstract:
Multiple myeloma (MM) is a hematological cancer characterized by accumulation of malignant plasma cells in the bone marrow. The patients are immune suppressed and suffer from recurrent and chronic infections. Interleukin-32 is a non-conventional, pro-inflammatory cytokine expressed in a subgroup of MM patients with a poor prognosis. IL-32 has also been shown to promote proliferation and survival of the cancer cells. Here we show that activation of toll-like receptors (TLRs) promotes expression of IL-32 in MM cells through NFκB activation. In patient-derived primary MM cells, IL-32 expression is positively associated with expression of TLRs. Furthermore, we found that several TLR genes are upregulated from diagnosis to relapse in individual patients, predominantly TLRs sensing bacterial components. Interestingly, upregulation of these TLRs coincides with an increase in IL-32. Taken together, these results support a role for IL-32 in microbial sensing in MM cells and suggest that infections can induce expression of this pro-tumorigenic cytokine in MM patients.
Insights
Toll-like receptor (TLR) activation boosts Interleukin-32 (IL-32) in multiple myeloma (MM) cells, potentially linking infections to cancer growth. Upregulated TLRs and IL-32 suggest a role in microbial sensing and disease progression.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Multiple myeloma (MM) is a bone marrow cancer with immune suppression, leading to frequent infections.
- Interleukin-32 (IL-32), a pro-inflammatory cytokine, is linked to poor prognosis in some MM patients and promotes cancer cell growth.
- The relationship between microbial sensing and IL-32 expression in MM remains unclear.
Purpose of the Study:
- To investigate the role of toll-like receptors (TLRs) in regulating IL-32 expression in multiple myeloma.
- To explore the association between TLRs, IL-32, and disease progression in MM patients.
Main Methods:
- Activation of TLRs in MM cells and assessment of IL-32 expression via NFκB signaling pathway.
- Analysis of IL-32 and TLR expression in patient-derived primary MM cells.
- Longitudinal analysis of TLR gene expression from MM diagnosis to relapse.
Main Results:
- TLR activation significantly increases IL-32 expression in MM cells through NFκB.
- A positive correlation exists between IL-32 and TLR expression in primary MM cells.
- TLR genes, particularly those sensing bacterial components, are upregulated from diagnosis to relapse, coinciding with increased IL-32 levels.
Conclusions:
- TLR activation is a key mechanism driving IL-32 expression in multiple myeloma.
- IL-32 may play a role in microbial sensing within MM cells.
- Infections could potentially induce pro-tumorigenic IL-32 in MM patients, highlighting a link between immunity and cancer progression.
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