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Interleukin-24: a molecule with potential anti-cancer activity and a cytokine in search of a function
Ali Dalloul1, Alexander Sainz-Perez
1Laboratory of cell therapy and University of Nancy - Medical school, Vandoeuvre les Nancy, France. a.dalloul@chu-nancy.fr
Abstract:
The gene encoding Melanoma-differentiation antigen-7 (MDA-7) was discovered more than 10 years ago. Its potential anti-cancer activity was surmised because its expression is inversely correlated with the cell proliferation status. Indeed adenoviral delivery of this gene proved to be efficient in killing several cancer cell lines and great strides have been made concerning its molecular ways of action. Later it was shown that mda7 encoded a secreted cytokine which belongs to the IL-10, class-II family of cytokines. We recently found that this molecule exerted apoptotic activity on stimulating but not on resting lymphocytes from a B cell leukaemia. This activity is distinct from that of intracellular MDA-7, and may pave the way for using the cytokine in cancers provided that they express the IL-24 Receptors; in this respect, melanomas are insensitive to the recombinant cytokine due to the lack of IL-24 receptors at their surface. In contrast to its anti-cancer activity, the immunological role of IL-24 is still unclear, with differences between mice and human. If however it is demonstrated that IL-24 can inhibit the function of STAT3 in normal lymphocytes as it is the case in leukemic cells, and given that STAT3 is needed for the differentiation of several lymphocyte subsets, this will give us hints as to the potential role of this cytokine in the immune system.
Insights
Melanoma-differentiation antigen-7 (MDA-7), now known as IL-24, shows anti-cancer properties by inducing apoptosis in certain cancer cells. Its precise role in the immune system, particularly in lymphocyte function, requires further investigation.
Area of Science:
- Immunology
- Molecular Biology
- Oncology
Background:
- Melanoma-differentiation antigen-7 (MDA-7) is a gene with known anti-cancer potential, linked to decreased cell proliferation.
- MDA-7 encodes a secreted cytokine, IL-24, belonging to the IL-10, class-II family.
- Previous research demonstrated adenoviral delivery of MDA-7 effectively kills various cancer cell lines.
Purpose of the Study:
- To investigate the apoptotic activity of the secreted cytokine IL-24 on lymphocytes.
- To explore the potential therapeutic applications of IL-24 in cancers expressing IL-24 receptors.
- To elucidate the immunological role of IL-24, particularly its effects on lymphocyte function and STAT3 signaling.
Main Methods:
- Adenoviral delivery of MDA-7/IL-24.
- Assessing apoptotic activity on stimulated and resting lymphocytes from B cell leukemia.
- Evaluating IL-24 receptor expression on cancer cells, including melanomas.
- Investigating potential inhibition of STAT3 function in lymphocytes.
Main Results:
- Secreted IL-24 demonstrated apoptotic activity on stimulated lymphocytes from B cell leukemia.
- Melanoma cells are insensitive to recombinant IL-24 due to a lack of IL-24 receptors.
- The anti-cancer activity of IL-24 is distinct from its intracellular form.
- The immunological role of IL-24 and its effects on STAT3 signaling in normal lymphocytes remain unclear.
Conclusions:
- Secreted IL-24 exhibits specific apoptotic effects on certain lymphocytes, suggesting potential cancer therapy applications for tumors expressing IL-24 receptors.
- The lack of IL-24 receptors on melanomas limits its direct therapeutic use in these cancers.
- Further research is needed to clarify the immunological functions of IL-24 and its impact on STAT3 signaling in normal lymphocytes, which could reveal its broader role in the immune system.
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