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Interleukin‐37 is highly expressed in regulatory T cells of melanoma patients and enhanced by melanoma cell secretome
Author(s) -
Osborne Douglas G.,
Domenico Joanne,
Luo Yuchun,
Reid Anna L.,
Amato Carol,
Zhai Zili,
Gao Dexiang,
Ziman Melanie,
Dinarello Charles A.,
Robinson William A.,
Fujita Mayumi
Publication year - 2019
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.23044
Subject(s) - biology , melanoma , immune system , immunology , downregulation and upregulation , cancer research , carcinogenesis , cancer , acquired immune system , gene , genetics
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 (T reg ) 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, T reg 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 T reg 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 T reg 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.