Interleukin-37 is highly expressed in regulatory T cells of melanoma patients and enhanced by melanoma cell secretome.

Abstract

Immune suppression is one of the 10 hallmarks of cancer. Interleukin-37 (IL-37), a member of the IL-1 family, inhibits both innate and adaptive immunity, and has been shown to modulate immune responses in various disease conditions. Yet, IL-37 has rarely been investigated in cancer patients, and its biological role in cancer remains to be elucidated. In this study, we investigated the gene expression of IL-37 in age- and sex-matched blood samples of healthy individuals and melanoma patients, and demonstrated upregulation of IL-37 messenger RNA (mRNA) in the blood samples of melanoma patients. By further analyzing immune cell subsets responsible for the upregulated IL-37 expression, we discovered that IL-37 mRNA was highly expressed in T cells and granulocytes, with the highest expression in regulatory T (Treg ) cells in healthy individuals, and that IL-37 mRNA was upregulated in lymphocytes (T, B, and natural killer cells) in melanoma patient blood. Among all cell subsets, Treg cells from melanoma patients exhibited the highest IL-37 gene expression levels. We provided evidence that melanoma-conditioned media induces IL-37 mRNA and protein expression in multiple lymphocyte populations, particularly in Treg cells. We further confirmed that the IL-1-mediated secretome from human melanoma cells, specifically transforming growth factor-β, induces IL-37 mRNA expression in human Treg cells. Our results suggest a potential immunosuppressive role for IL-1 and IL-37 in melanoma tumorigenesis. Highly elevated IL-37 in specific lymphocyte populations could serve as a biomarker for tumor-induced immunosuppression.

• Authors: Douglas G Osborne, Joanne Domenico, Yuchun Luo, Anna L Reid, Carol Amato, Zili Zhai, Dexiang Gao, Melanie Ziman, Charles A Dinarello, William A Robinson, Mayumi Fujita
• Journal: Molecular carcinogenesis (Mol Carcinog) Vol. 58 Issue 9 Pg. 1670-1679 (09 2019) ISSN: 1098-2744 [Electronic] United States
• PMID: 31099111 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2019 Wiley Periodicals, Inc.

Chemical References

• Biomarkers, Tumor
• IL37 protein, human
• Interleukin-1
• RNA, Messenger
• Transforming Growth Factor beta

Topics

• Biomarkers, Tumor (metabolism)
• Cells, Cultured
• Female
• Humans
• Interleukin-1 (metabolism)
• Male
• Melanoma (metabolism)
• RNA, Messenger (metabolism)
• T-Lymphocytes, Regulatory (metabolism)
• Transforming Growth Factor beta (metabolism)
• Up-Regulation (physiology)