The IL-33/ST2 pathway suppresses murine colon cancer growth and metastasis by upregulating CD40 L signaling - 30/05/20
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Graphical abstract |
Highlights |
• | IL-33 inhibits murine colon cancer growth and metastasis to lung and liver. |
• | IL-33-induced immune response is time-dependent and tissue-specific. |
• | CD4+ T cells are required for IL-33-mediated antitumor activity. |
• | IL-33 exerts antitumor efficacy by upregulating CD40 L signaling. |
• | IL-33 acts on CD4+ T cells via a positive-feedback loop. |
Abstract |
Interleukin (IL)-33 is a member of the IL-1 family, participating in both helper T1 (Th1)- and Th2-type immune responses, but its ambiguous effects on tumor growth and related immune mechanisms remain unclear. Here, we report that recombinant mouse IL-33 (mIL-33) significantly inhibited colon cancer growth and metastasis to lung and liver in a murine CT26 or MC38 tumor-cell engraftment model. This effect could be associated with CD4+ T cells and CD40 L signaling, as depletion of CD4+ T cells or blocking CD40 L signaling in vivo partly abolished the antitumor function of IL-33. In addition, IL-33 treatment upregulated CD40 L expression on tumor-infiltrating lymphocytes, and promoted the activation of CD4+ T, CD8+ T and natural killer cells via CD40 L signaling. Furthermore, IL-33 was sufficient to induce the ST2 expression on CD4+ T cells, but not on CD8+ T and natural killer cells, indicating that IL-33 acted on CD4+ T cells via a positive-feedback loop. Our findings shed new light on the IL-33-mediated antitumor effects and mechanisms of Th1 action, and also suggest that IL-33 may serve as an activator to boost anticancer immune responses in singular or combinatory therapies.
Le texte complet de cet article est disponible en PDF.Abbreviations : IL-33, mIL-33, ST2, PD-1, DC, NK, MHC, FBS, PBS, H&E, WT, MFI, MDSC, ILC2
Keywords : IL-33, ST2, CD40L signaling, Colorectal cancer, Cancer immunotherapy
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Article 110232- juillet 2020 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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