IL-33 restricts tumor growth and inhibits pulmonary metastasis in melanoma-bearing mice through eosinophils

V. Lucarini, G. Ziccheddu, I. Macchia, V. La Sorsa, F. Peschiaroli, C. Buccione, A. Sistigu, M. Sanchez, S. Andreone, M. T. D'Urso, M. Spada, D. Macchia, C. Afferni, F. Mattei, G. Schiavoni

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Abstract

The alarmin IL-33 is an IL-1 family member that stimulates pleiotropic immune reactions depending on the target tissue and microenvironmental factors. In this study, we have investigated the role of IL-33/ST2 axis in antitumor response to melanoma. Injection of IL-33 in mice-bearing subcutaneous B16.F10 melanoma resulted in significant tumor growth delay. This effect was associated with intratumoral accumulation of CD8+ T cells and eosinophils, decrease of immunosuppressive myeloid cells, and a mixed Th1/Th2 cytokine expression pattern with local and systemic activation of CD8+ T and NK cells. Moreover, intranasal administration of IL-33 determined ST2-dependent eosinophil recruitment in the lung that prevented the onset of pulmonary metastasis after intravenous injection of melanoma cells. Accordingly, ST2-deficient mice developed pulmonary metastasis at higher extent than wild-type counterparts, associated with lower eosinophil frequencies in the lung. Of note, depletion of eosinophils by in vivo treatment with anti-Siglec-F antibody abolished the ability of IL-33 to both restrict primary tumor growth and metastasis formation. Finally, we show that IL-33 is able to activate eosinophils resulting in efficient killing of target melanoma cells, suggesting a direct antitumor activity of eosinophils following IL-33 treatment. Our results advocate for an eosinophil-mediated antitumoral function of IL-33 against melanoma, thus opening perspectives for novel cancer immunotherapy strategies.
Original languageEnglish
Pages (from-to)e1317420
JournalOncoImmunology
Volume6
Issue number6
DOIs
Publication statusPublished - Apr 20 2017

Keywords

  • Eosinophils
  • interleukin (IL)-33
  • melanoma
  • mouse models
  • pulmonary metastasis

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    Lucarini, V., Ziccheddu, G., Macchia, I., Sorsa, V. L., Peschiaroli, F., Buccione, C., Sistigu, A., Sanchez, M., Andreone, S., D'Urso, M. T., Spada, M., Macchia, D., Afferni, C., Mattei, F., & Schiavoni, G. (2017). IL-33 restricts tumor growth and inhibits pulmonary metastasis in melanoma-bearing mice through eosinophils. OncoImmunology, 6(6), e1317420. https://doi.org/10.1080/2162402X.2017.1317420 [doi]