Please use this identifier to cite or link to this item: https://scidar.kg.ac.rs/handle/123456789/12777
Title: Interleukin-33 pretreatment promotes metastatic growth of murine melanoma by reducing the cytotoxic capacity of CD8<sup>+</sup> T cells and enhancing regulatory T cells
Authors: Jevtovic A.
Pantic, Jelena
Jovanovic I.
Milovanovic, Marija
Stanojevic, Ivan
Vojvodic, Danilo
Arsenijevic, Nebojsa
Lukic, Miodrag
Radosavljevic, Gordana
Journal: Cancer Immunology, Immunotherapy
Issue Date: 1-Aug-2020
Abstract: © 2020, Springer-Verlag GmbH Germany, part of Springer Nature. Interleukin-33 (IL-33) regulates innate and acquired immune response to pathogens, self-antigens and tumors. IL-33 effects on tumors depend on the dose and mode of administration along with the type of malignancy. We studied the effects of IL-33 on the development of primary and metastatic melanoma induced by B16-F1 cell line in C57BL/6 mice. Intraperitoneally applied IL-33 restricts primary tumor growth. When administered intranasally 3 days prior to the intravenous injection of the tumor cells, IL-33 promoted growth of B16-F1 melanoma metastases, while B16-F10 gave massive metastases independently of IL-33. To mimic natural dissemination, we next used a limited number (5 × 104) of B16-F1 cells intravenously followed by application of IL-33 intraperitoneally. IL-33 increased the size of metastases (10.96 ± 3.96 mm2) when compared to the control group (0.86 ± 0.39 mm2), without changing incidence and number of metastases. IL-33 increased expression of ST2 on both tumor and immune cells in metastases. Also, IL-33 enhanced eosinophils and anti-tumor NK cells in the lung. The striking finding was reduced cytotoxicity of CD8+ T cells derived from metastatic lung of IL-33 injected mice. IL-33 reduced the percentage of TNF-α+ and IFN-γ+ CD8+ T cells while increasing the frequency of CD8+ T cells that express inhibitory molecules (PD-1, KLRG-1 and CTLA-4). There was a significant accumulation of CD11b+Gr-1+ myeloid suppressor cells and FoxP3+, IL-10+ and CTLA-4+ regulatory T cells in the metastatic lung of IL-33 injected mice. The relevance of IL-33 for melanoma metastases was also documented in a significantly increased level of serum IL-33 in stage III melanoma patients.
URI: https://scidar.kg.ac.rs/handle/123456789/12777
Type: journal article
DOI: 10.1007/s00262-020-02522-x
ISSN: 03407004
SCOPUS: 85083287862
Appears in Collections:Faculty of Medical Sciences, Kragujevac

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