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IL-7 Receptor Blockade Inhibits IL-17-Producing γδ Cells and Suppresses Melanoma Development

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Abstract

In order to understand how tumor cells can escape immune surveillance mechanisms and thus develop antitumor therapies, it is critically important to investigate the mechanisms by which the immune system interacts with the tumor microenvironment. In our current study, wild-type mice are inoculated with melanoma cell line B16-F10 (1 × 106/mouse) and treated with anti-IL-7R antibody or recombined mouse IL-7 (rmIL-7). Growth of melanoma cell line B16-F10 was significantly inhibited in anti-IL-7R antibody-treated mice and markedly promoted in rmIL-7-treated mice compared with that in control. A decreased number of myeloid-derived suppressor cells (MDSCs) and γδ cells in tumor tissues were detected from anti-IL-7R antibody-treated mice. Next, administration of the anti-IL-7R antibody significantly blocked the enrichment in IL-17+ γδ cells in tumor. Moreover, in our further experiment, promoted melanoma development induced by rmIL-7 was abrogated with p-Stat3 inhibitor. The increased proportion and absolute number of IL-17-producing γδ27− cell induced by rmIL-7 were also abolished with the p-Stat3 inhibitor administration, and the suppressed melanoma development induced by anti-IL-7R antibody treatment was reversed with additional use of Ad-IL-17. In conclusion, IL-7/IL-7R-Stat3-IL-17 pathway promotes melanoma growth, and inhibition of IL-7/IL-7R-Stat3-IL-17 pathway may contribute to tumor growth in murine models of melanoma.

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Acknowledgments

This work was supported by National Natural Science Found of China Grants 81202335.

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Authors and Affiliations

  1. Department of Oncology, The Central Hospital of Wuhan, 26# Wuhan Shengli Road, Wuhan, Hubei, China

    Jun Li, Qiu Tang & Hongda Lu

  2. Department of Oncology, Wuhan General Hospital of Guangzhou Command, People’s Liberation Army, Wuhan, China

    Jian Liu

  3. Department of Gynaecology and Obstetrics, **angyan Central Hospital, Hubei University of Arts and Science, **angyang, Hubei, China

    **aogang Mao

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  1. Jun Li
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Correspondence to Jun Li.

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Li, J., Liu, J., Mao, X. et al. IL-7 Receptor Blockade Inhibits IL-17-Producing γδ Cells and Suppresses Melanoma Development. Inflammation 37, 1444–1452 (2014). https://doi.org/10.1007/s10753-014-9869-2

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